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The housing conditions of laboratory mice must be strictly controlled in order to reduce the impact of pathophysiological changes that affect animal health and welfare, possibly resulting in increased variability within experimental results. One way to improve the activity and survival of laboratory mice is to provide nesting material. The objective of this study was to determine if nest-building quality could be used to detect changes in murine mating behaviour in a rodent facility under controlled conditions. Nesting scores of 847 cages with monogamous pairs from three different genetic backgrounds (129, B6 and BALB/c) of both sexes were correlated with 18 predefined variables. The effects on nest quality were evaluated using descriptive data analysis, correspondence analysis and ordinal logistic model fitting. The results showed a strong relationship between nest quality and nest position. Humidity, genetic background, cage change and the number and age of pups in the cage affected the nest-building scores. The most important indicators were cage change and relative humidity, both of which exerted significant negative effects on nest-building quality. Even though the criteria were well defined, the observer could still influence nest score appraisal. However, in a long-term observational study, observers could improve their assessment by training and acquiring greater experience in score assignment. Nest-building scores are easy to assess in the cage, with little discomfort to the animal. Moreover, the nest score is a valid indicator of the health and well-being of laboratory mice and can provide valuable support in the management of animal facilities.
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Abrigo para Animais , Comportamento de Nidação , Animais , Feminino , Masculino , Camundongos/fisiologia , Camundongos Endogâmicos BALB C , Comportamento Sexual Animal/fisiologia , Criação de Animais Domésticos/métodos , Umidade , Bem-Estar do AnimalRESUMO
OBJECTIVE: Our study aimed to assess the impact of genetic modifiers on the significant variation in phenotype that is observed in individuals with SHOX deficiency, which is the most prevalent monogenic cause of short stature. DESIGN AND METHODS: We performed a genetic analysis in 98 individuals from 48 families with SHOX deficiency with a target panel designed to capture the entire SHOX genomic region and 114 other genes that modulate growth and/or SHOX action. We prioritized rare potentially deleterious variants. RESULTS: We did not identify potential deleterious variants in the promoter or intronic regions of the SHOX genomic locus. In contrast, we found eight heterozygous variants in 11 individuals from nine families in genes with a potential role as genetic modifiers. In addition to a previously described likely pathogenic (LP) variant in CYP26C1 observed in two families, we identified LP variants in PTHLH and ACAN, and variants of uncertain significance in NPR2, RUNX2, and TP53 in more affected individuals from families with SHOX deficiency. Families with a SHOX alteration restricted to the regulatory region had a higher prevalence of a second likely pathogenic variant (27%) than families with an alteration compromising the SHOX coding region (2.9%, P = .04). CONCLUSION: In conclusion, variants in genes related to the growth plate have a potential role as genetic modifiers of the phenotype in individuals with SHOX deficiency. In individuals with SHOX alterations restricted to the regulatory region, a second alteration could be critical to determine the penetrance and expression of the phenotype.
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Nanismo , Humanos , Íntrons , Genômica , Lâmina de Crescimento , Fenótipo , Doenças Raras , Proteína de Homoeobox de Baixa Estatura/genéticaRESUMO
We are all similar but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly, and yeast panels with insightful applications for translational research.
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Saccharomyces cerevisiae , Pesquisa Translacional Biomédica , Animais , Mapeamento Cromossômico , Patrimônio Genético , Genoma , Humanos , Camundongos , Saccharomyces cerevisiae/genéticaRESUMO
A number of genetic factors have been linked to the development of diabetes, a condition that often requires implantable devices such as glucose sensors. In normoglycaemic individuals, this procedure induces a foreign body reaction (FBR) that is detrimental to bioimplant functionality. However, the influence of the genetic background on this reaction in diabetes has not been investigated. We examined the components of FBR (capsule thickness, collagen deposition, mast cell and foreign body giant cell number) in subcutaneous implants of polyether polyurethane (SIPP) in streptozotocin (STZ)-induced diabetes in Swiss, C57BL/6 and Balb/c mice. The fasting blood glucose levels before STZ injections were 133.5 ± 5.1 mg/dL, after the treatment increased 68.4% in Swiss mice, 62.4% in C57BL/6 and 30.9% in Balb/c mice. All FBR features were higher in implants of Swiss and C57BL/6 mice compared with those in implants of Balb/c. Likewise, the apoptotic index was higher in implants of diabetic Swiss and C57BL/6 mice whose glycaemic levels were the highest. Our findings show an association between the severity of hyperglycaemic levels and the intensity of the FBR to SIPP. These important strain-related differences in susceptibility to diabetes and the intensity of the FBR must be considered in management using implantable devices in diabetic individuals.
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Diabetes Mellitus Experimental , Reação a Corpo Estranho , Patrimônio Genético , Próteses e Implantes , Animais , Materiais Biocompatíveis , Diabetes Mellitus Experimental/induzido quimicamente , Modelos Animais de Doenças , Fibrose , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , PoliuretanosRESUMO
RESUMEN El cáncer gástrico es una de las principales causas de muerte por neoplasias en el mundo. Las guías de prácticas clínicas actuales ofrecen modelos de tratamiento que involucran a la cirugía, radioterapia, quimioterapia, inmunoterapia y terapia dirigida a receptores de crecimiento específicos, sin embargo, los aspectos genéticos y de la biología molecular no siempre son tenidos en cuenta en la práctica médica. El objetivo de la presente revisión es articular los aspectos actuales más relevantes de la genética y la biología molecular en relación con el cáncer gástrico, para integrarlos en las guías clínicas de pacientes y familiares con el diagnóstico o con riesgo de padecer este tipo de neoplasia. Para ello se revisaron los avances genéticos y los síndromes relacionados con el cáncer gástrico, clasificaciones moleculares e implicaciones en su manejo. Se utilizaron las bases de datos Google Scholar, Elsevier y PubMed en los últimos 10 años, seleccionándose los de mayor importancia a texto completo desde el punto de vista cualitativo. La integración de antecedentes personales y familiares con elementos genéticos precisan ser tenidos en cuenta en el manejo, diagnóstico y prevención de esta enfermedad. Se sugiere la inclusión de elementos genéticos y moleculares en toda guía de práctica clínica.
ABSTRACT Gastric cancer is one of the leading causes of death from neoplasms in the world. Current clinical practice guidelines offer treatment models that involve surgery, radiotherapy, chemotherapy, immunotherapy and therapy directed at specific growth receptors, however, genetic and molecular biology aspects are not always taken into account in medical practice. The objective of this review is to articulate the most relevant current aspects of genetics and molecular biology in relation to gastric cancer, to integrate them into the clinical guidelines of patients and relatives with the diagnosis or at risk of suffering from this type of neoplasia. For them, genetic advances and syndromes related to gastric cancer, molecular classifications and implications in their management were reviewed. The databases Google Scholar, Elsevier, and PubMed were used in the last 10 years, selecting the most important full-text from a qualitative point of view. The integration of personal and family history with genetic elements needs to be taken into account in the diagnostic management and prevention of this disease. The inclusion of genetic and molecular elements in all clinical practice guidelines is suggested.
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There are more than 1000 odorant receptor (OR) genes in the mouse genome. Each olfactory sensory neuron expresses only one of these genes, in a monoallelic fashion. The transcript abundance of homologous OR genes vary between distinct mouse strains. Here we analyzed the expression of the OR gene Olfr17 (also named P2) in different genomic contexts. Olfr17 is expressed at higher levels in the olfactory epithelium from 129 mice than from C57BL/6 (B6) mice. However, we found that in P2-IRES-tauGFP knock-in mice, the transcript levels of the 129 Olfr17 allele are highly reduced when compared to the B6 Olfr17 allele. To address the mechanisms involved in this variation we compared the 5' region sequence and DNA methylation patterns of the B6 and 129 Olfr17 alleles. Our results show that genetic variations in cis regulatory regions can lead to differential DNA methylation frequencies in these OR gene alleles. They also show that expression of the Olfr17 alleles is largely affected by the genetic background, and suggest that in knock-in mice, expression can be affected by epigenetic modifications in the region of the targeted locus.
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Background: Considering the complexity of the factors involved in the immunopathology of Chagas disease, which influence the Chagas' disease pathogenesis, anti-T. cruzi immune response, and chemotherapy outcome, further studies are needed to improve our understanding about these relationships. On this way, in this article we analyzed the host genetic influence on hematological, histopathological and immunological aspects after T. cruzi infection. Methods: BALB/c and A mice were intragastrically infected with T. cruzi SC2005 strain, isolated from a patient of an outbreak of Chagas disease. Parameters such as parasite load, survival rates, cytokines production, macrophages, T and B cell frequencies, and histopathology analysis were carried out. Results: BALB/c mice presented higher parasitemia and mortality rates than A mice. Both mouse lineages exhibited hematological alterations suggestive of microcytic hypochromic anemia and histopathological alterations in stomach, heart and liver. The increase of CD8+ T cells, in heart, liver and blood, and the increase of CD19+ B cells, in liver, associated with a high level of proinflammatory cytokines (IL-6, TNF-α, IFN-γ), confer a resistance profile to the host. Although BALB/c animals exhibited the same findings observed in A mice, the response to infection occurred later, after a considerable parasitemia increase. By developing an early response to the infection, A mice were found to be less susceptible to T. cruzi SC2005 infection. Conclusions: Host genetics background shaping the response to infection. The early development of a cytotoxic cellular response profile with the production of proinflammatory cytokines is important to lead a less severe manifestation of Chagas disease.
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Doença de Chagas , Animais , Doença de Chagas/genética , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Citocinas/imunologia , Feminino , Coração/parasitologia , Fígado/parasitologia , Fígado/patologia , Camundongos Endogâmicos , Miocárdio/patologia , Carga Parasitária , Parasitemia/genética , Parasitemia/imunologia , Parasitemia/patologia , Especificidade da Espécie , Estômago/parasitologia , Estômago/patologiaRESUMO
Insect epidermal cells secrete a cuticle that serves as an exoskeleton providing mechanical rigidity to each individual, but also insulation, camouflage or communication within their environment. Cuticle deposition and hardening (sclerotization) and pigment synthesis are parallel processes requiring tyrosinase activity, which depends on an unidentified copper-dependent enzyme component in Drosophila melanogaster. We determined the metallomes of fly strains selected for lighter or darker cuticles in a laboratory evolution experiment, asking whether any specific element changed in abundance in concert with pigment deposition. The results showed a correlation between total iron content and strength of pigmentation, which was further corroborated by ferritin iron quantification. To ask if the observed increase in iron body content along with increased pigment deposition could be generalizable, we crossed yellow and ebony alleles causing light and dark pigmentation, respectively, into similar genetic backgrounds and measured their metallomes. Iron remained unaffected in the various mutants providing no support for a causative link between pigmentation and iron content. In contrast, the combined analysis of both experiments suggested instead a correlation between pigment deposition and total copper body content, possibly due to increased demand for epidermal tyrosinase activity.
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Cobre/análise , Drosophila melanogaster/química , Animais , Cobre/metabolismo , Drosophila melanogaster/metabolismo , Melaninas/análise , Melaninas/metabolismo , PigmentaçãoRESUMO
In order to preserve structure and function, proteins tend to preferentially conserve amino acids at particular sites along the sequence. Because mutations can affect structure and function, the question arises whether the preference of a protein site for a particular amino acid varies between protein homologs, and to what extent that variation depends on sequence divergence. Answering these questions can help in the development of models of sequence evolution, as well as provide insights on the dependence of the fitness effects of mutations on the genetic background of sequences, a phenomenon known as epistasis. Here, I comment on recent computational work providing a systematic analysis of the extent to which the amino acid preferences of proteins depend on the background mutations of protein homologs.
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BACKGROUND: Genetically engineered mice (GEM) are essential tools for understanding gene function and disease modeling. Historically, gene targeting was first done in embryonic stem cells (ESCs) derived from the 129 family of inbred strains, leading to a mixed background or congenic mice when crossed with C57BL/6 mice. Depending on the number of backcrosses and breeding strategies, genomic segments from 129-derived ESCs can be introgressed into the C57BL/6 genome, establishing a unique genetic makeup that needs characterization in order to obtain valid conclusions from experiments using GEM lines. Currently, SNP genotyping is used to detect the extent of 129-derived ESC genome introgression into C57BL/6 recipients; however, it fails to detect novel/rare variants. RESULTS: Here, we present a computational pipeline implemented in the Galaxy platform and in BASH/R script to determine genetic introgression of GEM using next generation sequencing data (NGS), such as whole genome sequencing (WGS), whole exome sequencing (WES) and RNA-Seq. The pipeline includes strategies to uncover variants linked to a targeted locus, genome-wide variant visualization, and the identification of potential modifier genes. Although these methods apply to congenic mice, they can also be used to describe variants fixed by genetic drift. As a proof of principle, we analyzed publicly available RNA-Seq data from five congenic knockout (KO) lines and our own RNA-Seq data from the Sall2 KO line. Additionally, we performed target validation using several genetics approaches. CONCLUSIONS: We revealed the impact of the 129-derived ESC genome introgression on gene expression, predicted potential modifier genes, and identified potential phenotypic interference in KO lines. Our results demonstrate that our new approach is an effective method to determine genetic introgression of GEM.
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Animais Geneticamente Modificados/genética , Patrimônio Genético , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Animais , Biologia Computacional , Inibidor de Quinase Dependente de Ciclina p21/genética , Proteínas de Ligação a DNA , Células-Tronco Embrionárias/fisiologia , Regulação da Expressão Gênica , Genes Modificadores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos da Linhagem 129 , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Análise de Sequência de RNA , Fatores de Transcrição , Sequenciamento do ExomaRESUMO
BACKGROUND: The effect of genetic background on the stability of fatty acid composition in sunflower near isogenic lines (NILs) carrying high-oleic Pervenets (P) or high-oleic NM1 mutations was studied. The materials were field-tested in different locations and at different sowing dates to evaluate a wide range of environmental conditions. Relationships were established between the fatty acids and the minimum night temperature (MNT) and the response was characterized. RESULTS: A genetic background effect for the fatty acid composition was found in both groups of NILs. The NM1-NILs showed an oleic level higher than 910 g kg-1 and they were more stable across environments with a zero or low dependence on the genetic background; on the other hand, high oleic materials bearing the P mutation showed lower levels of oleic acid, with a higher variation in fatty acid composition and a highly significant dependence on the genetic background. CONCLUSION: The NM1 mutation is the best option to develop ultra-high oleic sunflower oil that is stable across environments and genetic backgrounds, making its agronomical production more efficient and predictable. © 2018 Society of Chemical Industry.
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Ácidos Graxos/química , Helianthus/química , Helianthus/genética , Patrimônio Genético , Mutação , Óleos de Plantas/química , Sementes/química , Sementes/genéticaRESUMO
C57Bl/6J mice are the gold standard animal model of diet-induced obesity. These animals become obese with higher adiposity, blood fasting glucose, triglycerides, and total cholesterol when fed a high-fat diet (HFD). Conversely, the FVB/N mouse line is thought to be resistant to diet-induced obesity, with low or no weight gain and adiposity in response to a HFD In this study, we investigated whether FVB/N mice are resistant or susceptible to metabolic disorder that is promoted by a HFD Biometric parameters and blood chemistry were analyzed in C57Bl/6J and FVB/N mice that were fed a chow diet or HFD Glucose and insulin sensitivity were assessed by performing the glucose tolerance test and measuring serum insulin/glucose and homeostasis model assessment-insulin resistance. Metabolism-related gene expression was investigated by real-time reverse transcription polymerase chain reaction. Adipocyte morphology and liver steatosis were evaluated using standard histology. FVB/N mice had higher adiposity than C57Bl/6J mice that were fed a chow diet and were glucose intolerant. FVB/N mice that were fed a HFD presented higher insulin resistance and greater liver steatosis. Epididymal white adipose tissue exhibited severe inflammation in FVB/N mice that were fed a HFD The FVB/N mouse strain is suitable for studies of diet-induced obesity, and the apparent lack of a HFD-induced response may reveal several strain-specific events that are triggered by a HFD Further studies of the FVB/N background may shed light on the complex multifactorial symptoms of obesity and metabolic syndrome.
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Dieta Hiperlipídica/efeitos adversos , Camundongos Obesos/metabolismo , Obesidade/etiologia , Adiposidade , Animais , Glicemia/metabolismo , Modelos Animais de Doenças , Patrimônio Genético , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos/genética , Obesidade/genéticaRESUMO
Genetic susceptibility is associated with inflammation, neovascularization, and diabetes phenotypes. However, to what extent this susceptibility influences inflammatory angiogenesis in internal injuries in diabetes has not been fully investigated. Using the subcutaneous implantation of a synthetic matrix as an internal wound model in Swiss, C57BL/6 and Balb/c mice, we have studied inflammation, angiogenesis, and cytokine production in the fibrovascular tissue induced by implants in diabetic animals. The hyperglycemic levels (mg/dl) after the diabetogenic treatment were 455.0±15 in Swiss, 393.0±22 in C57BL/6, and 190.0±10 in Balb/c mice. Angiogenesis in Swiss implants from non-diabetic animals were higher than those in the implants from the other strains. However, the angiogenic inducers VEGF and nitric oxide (NO) were higher in implants from non-diabetic Swiss and Balb/c mice. Strain-related differences were also observed in the angiogenic parameters in implants from diabetic mice. Hb content and number of vessels decreased more than 40% in Swiss implants. In contrast, Hb content did not alter in implants from Balb/c diabetic mice and the number of vessels decreased. VEGF levels increased in implants from Swiss and C57BL/6 diabetic mice, but decreased in Balb/c implants. The levels of pro-inflammatory markers intra-implant also varied among the strains in both conditions. In the hyperglycemic environment, almost all inflammatory markers increased in implants from diabetic Swiss mice. These findings demonstrate the major contribution of genetic background in the pattern of inflammatory angiogenesis components of internal injury, in both normoglycemic and hyperglycemic animals.
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Diabetes Mellitus Experimental/patologia , Inflamação/patologia , Neovascularização Patológica/patologia , Ferimentos e Lesões/patologia , Animais , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/metabolismo , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Óxido Nítrico/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/fisiologia , Ferimentos e Lesões/metabolismoRESUMO
BACKGROUND/AIM: Preeclampsia is a leading cause of maternal death in the developing world. Our aim was to quantify and compare messenger (mRNA) expression of nuclear factor-kappa beta (NF-κΒ) and superoxide dismutase (SOD) in control patients with preeclampsia and without preeclampsia with or without familial hereditary background. MATERIALS AND METHODS: Four groups of patients were formed depending on the presence or absence of preeclampsia and presence or absence of familial history for preeclampsia. NF-κΒ and SOD were measured in human placentas by real-time quantitative polymerase chain reaction. The 2-ΔΔct analysis method was used to measure the difference in the relative expression of the target genes in each group of patients. RESULTS: In NF-κΒ expression, there was an increase of 23.35% in the group of women with preeclampsia versus women with preeclampsia without familial history. Regarding SOD, there was a reduction of about 33.33% in the expression in women with preeclampsia with familial history versus women with preeclampsia without familial history. CONCLUSION: Familial presence of preeclampsia could predispose to altered expression in SOD and NF-κΒ.
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Pré-Eclâmpsia , Feminino , Humanos , NF-kappa B , Placenta , Gravidez , RNA Mensageiro , Superóxido DismutaseRESUMO
M1 macrophages are more effective in the induction of the inflammatory response and clearance of Mycobacterium tuberculosis than M2 macrophages. Infected C57BL/6 mice generate a stronger cellular immune response compared with BALB/c mice. We hypothesized that infected C57BL/6 mice would exhibit a higher frequency and function of M1 macrophages than infected BALB/c mice. Our findings show a higher ratio of macrophages to M2 macrophages in the lungs of chronically infected C57BL/6 mice compared with BALB/c mice. However, there was no difference in the functional ability of M1 and M2 macrophages for the two strains in vitro. In vivo, a deleterious role for M2 macrophages was confirmed by M2 cell transfer, which rendered the infected C57BL/6, but not the BALB/c mice, more susceptible and resulted in mild lung inflammation compared with C57BL/6 mice that did not undergo cell transfer. M1 cell transfer induced a higher inflammatory response, although not protective, in infected BALB/c mice compared with their counterparts that did not undergo cell transfer. These findings demonstrate that an inflammation mediated by M1 macrophages may not induce bacterial tolerance because protection depends on the host genetic background, which drives the magnitude of the inflammatory response against M. tuberculosis in the pulmonary microenvironment. The contribution of our findings is that although M1 macrophage is an effector leucocyte with microbicidal machinery, its dominant role depends on the balance of M1 and M2 subsets, which is driven by the host genetic background.
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Pulmão/imunologia , Macrófagos/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Animais , Suscetibilidade a Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/enzimologia , Óxido Nítrico Sintase Tipo II/análise , Especificidade da EspécieRESUMO
Type 2 diabetes (T2D) is a complex disease caused by the interaction of genetic and environmental factors. In this regard, it has been demonstrated that Hispanics have a greater susceptibility to developing complex diseases like T2D, which has been attributed to their Amerindian component. Mexico has a wide population variety as a result of Amerindian (56-69%), European (26-41.8%) and African (1.8-6%) ancestral components. The stratification of the population has made difficult the study of T2D in the Mexican population. Despite advances, in Mexico the studies in this field are scarce; 9 of 88 loci associated with type 2 diabetes by genome-wide association studies (GWAS) in Caucasian populations have been replicated in the Mexican population. Currently, only 19 common variants and two variants of low frequency have been associated with T2D in Mexico. With respect to the private genetic variation in Mexican population, only one haplotype and two genetic variants have been described. This confirms the existence of new genetic variants not yet described, exclusive to the Mexican population, which suggests most likely, that there are more genetic variants to discover. Thus, in the present review we aim to bring together in one place all the studies about T2D in Mexico to understand the contribution of the genetic factors in the susceptibility to developing T2D in a Mexican population.
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Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/etnologia , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Americanos Mexicanos , México/epidemiologia , Risco , População BrancaRESUMO
In real food, starch is usually forming part of a matrix with lipids and proteins. However, research on this ternary system and interactions between such food components has been scarce so far. The control of food microstructure is crucial to determine the product properties, including sensorial and nutritionals ones. This paper reviews the microstructural principles of interactions between starch, lipids, and proteins in foods as well as their effect on postprandial glycemic response, considering human intrinsic differences on postprandial glycemic responses. Several lines of research support the hypothesis that foods without rapidly digestible starch will not mandatorily generate the lowest postprandial glycemic response, highlighting that the full understanding of food microstructure, which modulates starch digestion, plays a key role on food design from a nutritional viewpoint.
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Glicemia , Análise de Alimentos , Lipídeos/química , Proteínas/química , Amido/química , HumanosRESUMO
The magnitude of the cellular adaptive immune response is critical for the control of Mycobacterium tuberculosis infection in the chronic phase. In addition, the genetic background is equally important for resistance or susceptibility to tuberculosis. In this study, we addressed whether lung populations of dendritic cells, obtained from genetically different hosts, would play a role in the magnitude and function of CD4(+) populations generated after M. tuberculosis infection. Thirty days post-infection, C57BL/6 mice, which generate a stronger interferon-γ (IFN-γ)-mediated immune response than BALB/c mice, exhibited a higher number and frequency of lung CD11c(+) CD11b(-) CD103(+) cells compared with BALB/c mice, which exhibited a high frequency of lung CD11c(+) CD11b(+) CD103(-) cells. CD11c(+) CD11b(-) CD103(+) cells, purified from lungs of infected C57BL/6 mice, but not from infected BALB/c mice, induced a higher frequency of IFN-γ-producing or interleukin-17 (IL-17)-producing CD4(+) cells. Moreover, CD4(+) cells also arrive at the lung of C57BL/6 mice faster than in BALB/c mice. This pattern of immune response seems to be associated with higher gene expression for CCL4, CCL19, CCL20 and CCR5 in the lungs of infected C57BL/6 mice compared with infected BALB/c mice. The results described here show that the magnitude of IFN-γ-producing or IL-17-producing CD4(+) cells is dependent on CD11c(+) CD11b(-) CD103(+) cells, and this pattern of immune response is directly associated with the host genetic background. Therefore, differences in the genetic background contribute to the identification of immunological biomarkers that can be used to design human assays to predict progression of M. tuberculosis infection.
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Antígenos CD/imunologia , Antígeno CD11c/imunologia , Cadeias alfa de Integrinas/imunologia , Interferon gama/imunologia , Interleucina-17/imunologia , Pulmão/imunologia , Mycobacterium tuberculosis/imunologia , Células Th17/imunologia , Tuberculose Pulmonar/imunologia , Animais , Antígenos CD/metabolismo , Antígeno CD11b/imunologia , Antígeno CD11b/metabolismo , Antígeno CD11c/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/microbiologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/microbiologia , Modelos Animais de Doenças , Feminino , Genótipo , Imunidade Celular , Cadeias alfa de Integrinas/metabolismo , Interferon gama/metabolismo , Interleucina-17/metabolismo , Pulmão/metabolismo , Pulmão/microbiologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/patogenicidade , Fenótipo , Transdução de Sinais , Especificidade da Espécie , Células Th17/metabolismo , Células Th17/microbiologia , Fatores de Tempo , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/metabolismo , Tuberculose Pulmonar/microbiologiaRESUMO
Individual kernel weight is an important trait for maize yield determination. We have identified genomic regions controlling this trait by using the B73xMo17 population; however, the effect of genetic background on control of this complex trait and its physiological components is not yet known. The objective of this study was to understand how genetic background affected our previous results. Two nested stable recombinant inbred line populations (N209xMo17 and R18xMo17) were designed for this purpose. A total of 408 recombinant inbred lines were genotyped and phenotyped at two environments for kernel weight and five other traits related to kernel growth and development. All traits showed very high and significant (P < 0.001) phenotypic variability and medium-to-high heritability (0.60-0.90). When N209xMo17 and R18xMo17 were analyzed separately, a total of 23 environmentally stable quantitative trait loci (QTL) and five epistatic interactions were detected for N209xMo17. For R18xMo17, 59 environmentally stable QTL and 17 epistatic interactions were detected. A joint analysis detected 14 stable QTL regardless of the genetic background. Between 57 and 83% of detected QTL were population specific, denoting medium-to-high genetic background effects. This percentage was dependent on the trait. A meta-analysis including our previous B73xMo17 results identified five relevant genomic regions deserving further characterization. In summary, our grain filling traits were dominated by small additive QTL with several epistatic and few environmental interactions and medium-to-high genetic background effects. This study demonstrates that the number of detected QTL and additive effects for different physiologically related grain filling traits need to be understood relative to the specific germplasm.
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Locos de Características Quantitativas , Zea mays/crescimento & desenvolvimento , Zea mays/genética , Mapeamento Cromossômico , Genótipo , Fenótipo , Sementes/genética , Sementes/crescimento & desenvolvimentoRESUMO
Type-1 (T1R) and Type-2 (T2R) leprosy reactions (LR), which affect up to 50% of leprosy patients, are aggressive inflammatory episodes of sudden onset and highly variable incidence across populations. LR are often diagnosed concurrently with leprosy, but more frequently occur several months after treatment onset. It is not uncommon for leprosy patients to develop recurring reactional episodes; however, they rarely undergo both types of LR. Today, LR are the main cause of permanent disabilities associated with leprosy and represent a major challenge in the clinical management of leprosy patients. Although progress has been made in understanding the immunopathology of LR, the factors that cause a leprosy patient to suffer from LR are largely unknown. Given the impact that ethnic background has on the risk of developing LR, host genetic factors have long been suspected of contributing to LR. Indeed, polymorphisms in seven genes [Toll-like receptors (TLR)1, TLR2, nucleotide-binding oligomerisation domain containing 2, vitamin D receptor, natural resistance-associated macrophage protein 1, C4B and interleukin-6] have been found to be associated with one or more LR outcomes. The identification of host genetic markers with predictive value for LR would have a major impact on nerve damage control in leprosy. In this review, we present the recent advances achieved through genetic studies of LR.