RESUMEN

Homozygous Dab1 yotari mutant mice, Dab1yot (yot/yot) mice, have an autosomal recessive mutation of Dab1 and show reeler-like phenotype including histological abnormality of the cerebellum, hippocampus, and cerebral cortex. We here show abnormal hippocampal development of yot/yot mice where granule cells and pyramidal cells fail to form orderly rows but are dispersed diffusely in vague multiplicative layers. Possibly due to the positioning failure of granule cells and pyramidal cells and insufficient synaptogenesis, axons of the granule cells did not extend purposefully to connect with neighboring regions in yot/yot mice. We found that both hippocampal granule cells and pyramidal cells of yot/yot mice expressed proteins reactive with the anti-Dab1 antibody. We found that Y198- phosphorylated Dab1 of yot/yot mice was greatly decreased. Accordingly the downstream molecule, Akt was hardly phosphorylated. Especially, synapse formation was defective and the distribution of neurons was scattered in hippocampus of yot/yot mice. Some of neural cell adhesion molecules and hippocampus associated transcription factors of the neurons were expressed aberrantly, suggesting that the Reelin-Dab1 signaling pathway seemed to be importantly involved in not only neural migration as having been shown previously but also neural maturation and/or synaptogenesis of the mice. It is interesting to clarify whether the defective neural maturation is a direct consequence of the dysfunctional Dab1, or alternatively secondarily due to the Reelin-Dab1 intracellular signaling pathways.

Asunto(s)

Moléculas de Adhesión Celular Neuronal/fisiología , Proteínas de la Matriz Extracelular/fisiología , Hipocampo/anomalías , Ratones Mutantes/anomalías , Proteínas del Tejido Nervioso/fisiología , Serina Endopeptidasas/fisiología , Transducción de Señal/fisiología , Animales , Moléculas de Adhesión Celular Neuronal/deficiencia , Movimiento Celular , Activación Enzimática , Proteínas de la Matriz Extracelular/deficiencia , Genes Recesivos , Hipocampo/embriología , Hipocampo/metabolismo , Hipocampo/patología , Homocigoto , Ratones , Ratones Mutantes/genética , Ratones Mutantes/metabolismo , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/deficiencia , Proteínas del Tejido Nervioso/genética , Moléculas de Adhesión de Célula Nerviosa/biosíntesis , Moléculas de Adhesión de Célula Nerviosa/genética , Fenotipo , Fosforilación , Procesamiento Proteico-Postraduccional , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína Reelina , Serina Endopeptidasas/deficiencia , Sinapsis/metabolismo , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética

RESUMEN

The Notch pathway, although originally identified in fruit flies, is now among the most heavily studied in mammalian biology. In mice, loss-of-function and gain-of-function work has demonstrated that Notch signaling is essential both during development and in the adult in a multitude of tissues. Prominent among these is the CNS, where Notch has been implicated in processes ranging from neural stem cell regulation to learning and memory. Here we review the role of Notch in the mammalian CNS by focusing specifically on mutations generated in mice. These mutations have provided critical insight into Notch function in the CNS and have led to the identification of promising new directions that are likely to generate important discoveries in the future.

Asunto(s)

Diferenciación Celular/genética , Sistema Nervioso Central/embriología , Regulación del Desarrollo de la Expresión Génica/genética , Malformaciones del Sistema Nervioso/genética , Receptores de Superficie Celular/metabolismo , Factores de Transcripción/metabolismo , Animales , Sistema Nervioso Central/crecimiento & desarrollo , Sistema Nervioso Central/metabolismo , Humanos , Ratones , Ratones Mutantes/anomalías , Ratones Mutantes/genética , Ratones Mutantes/metabolismo , Mutación/genética , Malformaciones del Sistema Nervioso/metabolismo , Malformaciones del Sistema Nervioso/fisiopatología , Receptor Notch1 , Receptores de Superficie Celular/genética , Transducción de Señal/genética , Células Madre/citología , Células Madre/metabolismo , Factores de Transcripción/genética

RESUMEN

While the role of the mutated Huntington's disease (HD) protein in the pathogenesis of HD has been the focus of intensive investigation, the normal protein has received less attention. Nonetheless, the wild-type HD protein appears to be essential for embryogenesis, since deletion of the HD gene in mice results in early embryonic lethality. This early lethality is due to a critical role the HD protein, called huntingtin (Htt), plays in extraembryonic membrane function, presumably in vesicular transport of nutrients. Studies of mutant mice expressing low levels of Htt and of chimeric mice generated by blastocyst injection of Hdh-/- embryonic stem cells show that wildtype Htt plays an important role later in development as well, specifically in forebrain formation. Moreover, various lines of study suggest that normal Htt is also critical for survival of neurons in the adult forebrain. The observation that Htt plays its key developmental and survival roles in those brain areas most affected in HD raises the possibility that a subtle loss of function on the part of the mutant protein or a sequestering of wild-type Htt by mutant Htt may contribute to HD pathogenesis. Regardless of whether this is so, the prosurvival role of Htt suggests that HD therapies that block production of both wild-type and mutant Htt may themselves be harmful.

Asunto(s)

Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Proteínas del Tejido Nervioso/fisiología , Neuronas/metabolismo , Proteínas Nucleares/fisiología , Animales , Transporte Biológico/fisiología , Encéfalo/embriología , Supervivencia Celular/genética , Modelos Animales de Enfermedad , Humanos , Proteína Huntingtina , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Ratones , Ratones Mutantes/anomalías , Ratones Mutantes/genética , Ratones Mutantes/metabolismo , Mutación/genética , Proteínas del Tejido Nervioso/genética , Neuronas/citología , Proteínas Nucleares/genética

RESUMEN

Defolliculated is a novel spontaneous mouse mutation that maps to chromosome 11 close to the type I keratin locus. Histology shows abnormal differentiation of the sebaceous gland, with the sebocytes producing little or no sebum and undergoing abnormal cornification. The hair follicles fail to regress during catagen leading to abnormally long follicles. In contrast the hair shafts are shorter than normal, suggesting altered differentiation or proliferation of matrix cells during anagen. The shafts emerge from the follicle with cornified material still attached. The dermis contains increased numbers of immune cells, including T cells (CD4-positive), macrophages, and mast cells, at all time points examined. Complete elimination of all pelage and tail follicles occurs after two to three hair cycles, apparently by necrosis. Defolliculated may be a useful model for determining further functions of the sebaceous gland, and for understanding the regulation of catagen and hair follicle immunology.

Asunto(s)

Alopecia/genética , Alopecia/patología , Folículo Piloso/anomalías , Ratones Mutantes/anomalías , Glándulas Sebáceas/anomalías , Animales , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Cromosomas , Epidermis/anomalías , Epidermis/inmunología , Epidermis/patología , Genes Dominantes , Folículo Piloso/inmunología , Folículo Piloso/patología , Ratones , Ratones Endogámicos BALB C , Fenotipo , Glándulas Sebáceas/inmunología , Glándulas Sebáceas/patología

RESUMEN

The osteopetrotic grey-lethal (gl) mouse mutant displays many similarities to the human malignant autosomal-recessive form of osteopetrosis. In this study, we show that the gl osteopetrotic bone phenotype is characterized by the presence of numerous differentiated multinucleated osteoclasts. A significant increase in the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was detected in vivo, suggesting induction of differentiation in the osteoclast lineage as a compensatory mechanism. These gl osteoclast cells demonstrated a defective cytoskeletal reorganization and an underdeveloped ruffled border, a membrane structure essential for active bone resorption. Accordingly, resorption activity of these cells is markedly impaired by four- to tenfold as evaluated with the pit formation assay. This low bone resorption in gl osteoclasts is highly reminiscent of the loss in key enzymes, V-ATPase or cathepsin-K, and in signaling factors, Src or TRAF-6, which were shown not to be significantly altered in gl osteoclasts. Thus, independently of a deficiency in V-ATPase, Src, cathepsin-K, and TRAF-6, the gl mutation results in increased number of osteoclasts, characterized by a disrupted cytoskeleton and an underdeveloped ruffled border.

Asunto(s)

Resorción Ósea/genética , Huesos/patología , Diferenciación Celular/genética , Ratones Mutantes/anomalías , Mutación/fisiología , Osteoclastos/patología , Osteopetrosis/patología , ATPasas de Translocación de Protón Vacuolares , Fosfatasa Ácida/metabolismo , Animales , Resorción Ósea/metabolismo , Resorción Ósea/patología , Huesos/metabolismo , Huesos/fisiopatología , Células Cultivadas/citología , Células Cultivadas/metabolismo , Técnicas de Cocultivo , Proteínas del Citoesqueleto/metabolismo , Citoesqueleto/metabolismo , Citoesqueleto/patología , Citoesqueleto/ultraestructura , Modelos Animales de Enfermedad , Genes Letales/fisiología , Inmunohistoquímica , Isoenzimas/metabolismo , Ratones , Ratones Mutantes/metabolismo , Microscopía Electrónica , Osteoclastos/metabolismo , Osteoclastos/ultraestructura , Osteopetrosis/genética , Osteopetrosis/fisiopatología , Fenotipo , Proteínas/metabolismo , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , ATPasas de Translocación de Protón/metabolismo , Factor 6 Asociado a Receptor de TNF , Fosfatasa Ácida Tartratorresistente

RESUMEN

Amperometry is a very powerful technique for investigating the role(s) specific proteins play in exocytosis at the single-cell level. In this study, amperometry has been used to investigate possible changes in exocytosis at chromaffin cells isolated from coloboma and tottering mutant mice. Coloboma mice possess a deletion mutation that encompasses the gene for the presynaptic protein SNAP-25 and tottering mice carry a mutation of the alpha(1A) subunit gene, which encodes the pore-forming region of P/Q-type calcium channels. Although amperometric data measured from tottering and coloboma cells are not significantly different from that measured at wild-type control cells, significant differences are found when groups of wild-type chromaffin cells are analyzed at room temperature and at 37 degrees C. Due to the large variability inherent to amperometric data, it is possible that changes in release resulting from some genetic differences cannot be detected. To fully exploit the technical advantages of using mouse chromaffin cells, experimental guidelines are described which should maximize changes in release resulting from genetic differences and increase the likelihood of detecting a change in amperometric data.

Asunto(s)

Células Cromafines/metabolismo , Electrofisiología/métodos , Exocitosis/genética , Proteínas de la Membrana/metabolismo , Ratones Mutantes/anomalías , Neurotransmisores/metabolismo , Animales , Canales de Calcio Tipo P/deficiencia , Canales de Calcio Tipo P/genética , Canales de Calcio Tipo Q/deficiencia , Canales de Calcio Tipo Q/genética , Células Cultivadas/metabolismo , Ratones , Ratones Mutantes/genética , Ratones Mutantes/metabolismo , Microelectrodos , Proteínas del Tejido Nervioso/deficiencia , Proteínas del Tejido Nervioso/genética , Proteína 25 Asociada a Sinaptosomas

RESUMEN

Mice lacking p35, an activator of cdk5 in the central nervous system (CNS), exhibit defects in a variety of CNS structures, most prominently characterized by a disruption in the laminar structure of the neocortex (Chae et al., 1997). In addition, alterations of certain axonal fiber tracts are found in the cortex of p35 mutant mice. Notably, the corpus callosum appears bundled at the midline, but dispersed lateral to the midline. Tracer injection experiments in adult p35 mutant mice reveal that projecting cortical axons fail to assimilate into the corpus callosum, and take oblique paths to the midline. After crossing the midline, cortical axons defasciculate prematurely from the corpus callosum and take similarly oblique paths through the cortex. This callosal phenotype is not detected in reeler mice, which also exhibit defects in cortical lamination, suggesting that the lack of fasciculation of callosal axons is not an inherent manifestation of a disruption of cortical lamination. The embryonic callosal axon tract is defasciculated before crossing the midline, suggesting that axon guidance may be affected during embryonic development of the corpus callosum. In addition, embryonic thalamocortical afferents also exhibit a defasciculated phenotype. These results suggest that defective axonal fasciculation and guidance may be primary responses to the loss of p35 in the cortex. Furthermore, this study postulates a role for the p35/cdk5 kinase in molecular signaling pathways necessary for proper guidance of selective axons during embryonic development.

Asunto(s)

Agenesia del Cuerpo Calloso , Axones/fisiología , Proteínas de la Membrana Bacteriana Externa/genética , Cuerpo Calloso/citología , Lipoproteínas/genética , Ratones Noqueados/anomalías , Fosfotransferasas , Animales , Axones/ultraestructura , Carbocianinas , Quinasa 5 Dependiente de la Ciclina , Quinasas Ciclina-Dependientes/fisiología , Inmunohistoquímica , Ratones , Ratones Mutantes/anomalías , Ratones Mutantes Neurológicos/anomalías , Vías Nerviosas/anomalías , Vías Nerviosas/citología , Corteza Somatosensorial/anomalías , Corteza Somatosensorial/citología , Tálamo/anomalías , Tálamo/citología

RESUMEN

The Snell dwarf mouse (Pit1dw-J homozygote) has a mutation in the Pit1 gene that prevents the normal formation of the anterior pituitary. In neonates and adults there is almost complete absence of growth hormone (GH), prolactin (PRL), thyroxin (T4), and thyroid-stimulating hormone (TSH). Since these hormones have been suggested to play a role in normal development of the central nervous system (CNS), we have investigated the effects of the Pit1dw-J mutation on the cerebellum and hippocampal formation. In the cerebellum, there were abnormalities of both foliation and lamination. The major foliation anomalies were 1) changes in the relative size of specific folia and also the proportional sizes of the anterior vs posterior cerebellum; and 2) the presence of between one and three microfolia per half cerebellum. The microfolia were all in the medial portion of the hemisphere in the caudal part of the cerebellum. Each microfolium was just rostral to a normal fissure and interposed between the fissure and a normal gyrus. Lamination abnormalities included an increase in the number of single ectopic granule cells in the molecular layer in both cerebellar vermis (86%) and hemisphere (40%) in comparison with the wild-type mouse. In the hippocampus of the Pit1dw-J homozygote mouse, the number of pyramidal cells was decreased, although the width of the pyramidal cell layer throughout areas CA1-CA3 appeared to be normal, but less densely populated than in the wild-type mouse. Moreover, the number of granule cells that form the granule cell layer was decreased from the wild-type mouse and some ectopic granule cells (occurring both as single cells and as small clusters) were observed in the innermost portion of the molecular layer. The abnormalities observed in the Pit1dw-J homozygote mouse seem to be caused by both direct and indirect effects of the deficiency of TSH (or T4), PRL, or GH rather than by a direct effect of the deletion of Pit1.

Asunto(s)

Movimiento Celular/fisiología , Corteza Cerebelosa/anomalías , Proteínas de Unión al ADN/genética , Ratones Mutantes/anomalías , Células Piramidales/citología , Factores de Transcripción/genética , Animales , Corteza Cerebelosa/citología , Giro Dentado/citología , Proteínas de Homeodominio/genética , Homocigoto , Ratones , Ratones Endogámicos C3H , Hipófisis/citología , Células Piramidales/química , Factor de Transcripción Pit-1

RESUMEN

The knotty-tail (knt/knt) mouse has a short and knotty tail. The tail deformity is caused by a decrease in the number of caudal vertebrae and a deformity of them in the distal part of the tail. The objective of the study was to determine how reduction and kinks of the tail region were formed during secondary body formation. By day 12.0 pc, the somitogenesis of knt/knt embryos was completed; the number of caudal somites more or less agreed with those of the caudal vertebrae in knt/knt mice and were similar to those of knt/+ embryos. On the other hand, the somitogenesis of knt/+ embryos continued up to day 12.5 pc. The somites below about the sixth caudal somite were wedge-shaped with a dorsal apex in knt/knt embryos. The location of abnormal somites also corresponded well to that of deformed caudal vertebrae. Abnormal somitogenesis was always preceded by abnormalities in the presomitic region. Under gross observation, this could be seen to become markedly thickened, and histologically its dorsoventral diameter increased in the transverse plane on days 10.5-12.0 pc. In the mesenchyme there was often obvious cell death at the boundary of the unsegmented area and the tail bud after day 10.5 pc. These results suggested that the shortness of tail was primarily caused by the agenesis of distal caudal vertebrae following the agenesis of distal caudal somites, and partly by the disappearance of the presomitic part due to cell death, while the tail kinks were caused by the deformation of each caudal vertebra following disturbances of the caudal somites. Also, it is highly probable that the prominent cell death at the boundary of the unsegmented area and the tail bud may involve a defect or deformity of somites in this mutant.

Asunto(s)

Ratones Mutantes/anatomía & histología , Columna Vertebral/anomalías , Cola (estructura animal)/anomalías , Animales , Cruzamiento , Ectodermo/citología , Femenino , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Mutantes/anomalías , Ratones Mutantes/genética , Morfogénesis , Defectos del Tubo Neural/genética , Notocorda/anomalías , Embarazo , Somitos/citología , Columna Vertebral/anatomía & histología , Cola (estructura animal)/anatomía & histología

RESUMEN

The sense of balance is one of the phylogenetically oldest sensory systems. The vestibular organs, consisting of sensory hair cells and an overlying extracellular membrane, have been conserved throughout vertebrate evolution. To better understand mechanisms regulating vestibular development and mechanisms of vestibular pathophysiology, we have analyzed the mouse mutant, tilted (tlt), which has dysfunction of the gravity receptors. The tilted mouse arose spontaneously and has not been previously analyzed for a developmental or physiological deficit. Here we demonstrate that the tilted mouse, like the head tilt (het) mouse, specifically lacks otoconia and consequently does not sense spatial orientation relative to the force of gravity. Unlike other mouse mutations affecting the vestibular system (such as pallid, mocha and tilted head), the defect in the tilted mouse is highly penetrant, results in the nearly complete absence of otoconia, exhibits no degeneration of the sensory epithelium and has no apparent abnormal phenotype in other organ systems. We further demonstrate that protein expression in the macular sensory epithelium is qualitatively unaltered in tilted mutant mice.

Asunto(s)

Umbral Auditivo/fisiología , Glicoproteínas/biosíntesis , Inclinación de Cabeza , Ratones Mutantes/anomalías , Membrana Otolítica/anomalías , Animales , Epitelio/fisiopatología , Potenciales Evocados Auditivos del Tronco Encefálico/genética , Femenino , Glicoproteínas/análisis , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes/genética , Microscopía Electrónica , Mutación/fisiología , Órgano Espiral/fisiopatología , Membrana Otolítica/fisiopatología , Membrana Otolítica/ultraestructura , Fenotipo , Equilibrio Postural/fisiología

RESUMEN

Familial hypobetalipoproteinemia (FHbeta), a syndrome characterized by low plasma cholesterol levels, is caused by mutations in the apo-B gene that interfere with the synthesis of apo-B100. FHbeta mutations frequently lead to the synthesis of a truncated form of apo-B, which typically is present in plasma at < 5% of the levels of apo-B100. Although many FHbeta mutations have been characterized, the basic mechanisms causing the low plasma levels of truncated apo-B variants have not been defined. We used gene targeting to create a mutant allele that exclusively yields a truncated apo-B, apo-B83. In mice heterozygous for the Apob83 allele, plasma levels and the size and density distribution of apo-B83-containing lipoproteins were strikingly similar to those observed in humans with FHbeta and an apo-B83 mutation. Analysis of mice carrying the Apob83 mutation revealed two mechanisms for the low plasma levels of apo-B83. First, Apob83 mRNA levels and apo-B83 secretion were reduced 76 and 72%, respectively. Second, apo-B83 was removed rapidly from the plasma, compared with apo-B100. This mouse model provides a new level of understanding of FHbeta and adds new insights into apo-B metabolism.

Asunto(s)

Apolipoproteínas B/biosíntesis , Apolipoproteínas B/genética , Hipobetalipoproteinemias/genética , Hipobetalipoproteinemias/metabolismo , Alelos , Animales , Apolipoproteína B-100 , Apolipoproteínas B/metabolismo , Apolipoproteínas E/fisiología , Colesterol/sangre , Clonación Molecular , ADN Complementario/genética , Mucosa Intestinal/metabolismo , Lipoproteínas HDL/análisis , Lipoproteínas HDL/sangre , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/análisis , Lipoproteínas LDL/sangre , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/análisis , Lipoproteínas VLDL/sangre , Lipoproteínas VLDL/metabolismo , Hígado/citología , Hígado/metabolismo , Ratones , Ratones Mutantes/anomalías , Mutagénesis Sitio-Dirigida , Linaje , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Receptores de LDL/fisiología , Transcripción Genética

RESUMEN

Analysis of the skeletal effects of thick tail (Tht), a radiation-induced mutation, has revealed numerous anomalies in the axial skeleton. The affected regions include the atlantal-occipital region as well as the lumbar (Lu) and caudal (Ca) vertebrae in which the ossified adult structures are either missing or reduced in size. Skeletons of juvenile Tht heterozygotes exhibit a malformed occipital bone, atlas, smaller Ca vertebrae, and delayed ossification of the affected adult structures. The diminished amount of cartilage and bone suggests that the Tht gene may be functioning during the formation of these tissues.

Asunto(s)

Ratones Mutantes/anomalías , Mutagénesis , Cráneo/anomalías , Médula Espinal/anomalías , Cola (estructura animal)/anomalías , Animales , Cartílago/anomalías , Cruzamientos Genéticos , Femenino , Tamización de Portadores Genéticos , Genotipo , Masculino , Ratones , Ratones Endogámicos , Ratones Mutantes/genética , Cráneo/efectos de la radiación , Médula Espinal/efectos de la radiación

RESUMEN

The lurcher mutation induces Purkinje cell degeneration in heterozygous mice, and neonatal death in homozygous animals. Using the D6Mit16 Simple Sequence Length Polymorphic marker in F2 hybrids between AKR +/+ mice and B6+/Lc mice, homozygous lurcher fetuses and newborns as well as heterozygous and normal littermates were identified, and their brain morphology was analysed. In homozygous lurcher embryos at embryonic day 18 and neonates the cerebellum was hypotrophic, particularly in the posterior half. Purkinje cells were smaller in the whole cerebellum and showed a maturational delay. Calretinin-positive cells were less frequently observed in the depth of the vermis than in normal mice. Both Purkinje cells and the vermal calretinin-positive cells were more abnormal in fetuses at day 19 and newborn mutants than one day earlier. An abnormal number of pycnotic cells were observed in the cerebellum, especially in newborn mutants. Brainstem abnormalities were characterized by abnormal curvature, caudal displacement of the pontine gray nuclei which were located caudally along the ventral border of the superior olivary complex, a drastic decrease in Purkinje cell axons in all the vestibular nuclei and the presence of dystrophic processes in at least two calbindin-positive cell groups of the dorsal pontine region. These results show that the mutation, which is semidominant in Purkinje cells, is recessive in other cell groups of the cerebellum and brainstem. They reveal that the sequence leading to Purkinje cell death appears to be similar in homozygous and heterozygous mice, although occurring earlier and worsening more quickly in the former. Lastly, they confirm the absence of effect of the mutation on the neurons of the inferior olivary complex.

Asunto(s)

Tronco Encefálico/anomalías , Cerebelo/anomalías , Ratones Mutantes/anomalías , Animales , Mapeo Encefálico , Inmunohistoquímica , Ratones

RESUMEN

kreisler is a recessive mutation resulting in gross malformation of the inner ear of homozygous mice. The defects in the inner ear are related to abnormalities in the hindbrain of the embryo, adjacent to the ear rudiments. At E9.5, the neural tube posterior to the boundary between the third and fourth rhombomeres, r3 and r4, appears unsegmented, and the region that would normally correspond to r4 is unusually thick-walled and contains many dying cells. The absence of morphological segmentation in the posterior hindbrain corresponds to an altered pattern of gene expression in that region, with major abnormalities posterior to the r4/5 boundary and minor abnormalities anterior to it. From the expression patterns at E9.5 of Krox-20, Hoxb-1 (Hox 2.9), Hoxb-2 (Hox 2.8), Hoxa-3 (Hox 1.5), Hoxd-4 (Hox 4.2) and cellular retinoic-acid binding protein I (CRABP I), it appears that the fundamental defect is a loss of r5 and r6. Correspondingly, the glossopharyngeal ganglion and nerve, associated with r6 are missing and the abducens nerve, which originates from r5 and r6, is also absent. Examination of Krox-20 expression at stages as early as E8.5 indicates that Krox-20 fails ever to be expressed in its r5 domain in the homozygous kreisler mutant. The abnormal amount of cell death is seen only later. An interpretation is that the cells that would normally become specified at an early stage as r5 and r6 adopt an r4 character instead, producing an excess of r4 cells that is disposed of subsequently by cell death.

Asunto(s)

Oído Interno/anomalías , Genes Homeobox/fisiología , Ratones Mutantes/anomalías , Rombencéfalo/anomalías , Animales , Muerte Celular/fisiología , Nervios Craneales/anomalías , Expresión Génica/fisiología , Ratones , Ratones Mutantes/embriología , Ratones Mutantes/genética

RESUMEN

The purpose of this study was to determine quantitatively whether the Br mouse displays craniofacial size and shape patterns indicative of midfacial retrusion. Fifteen craniometric variables derived from a total of 40 male and female Br mice were compared with an equivalent number of C3H/HeJ adult mice displaying normal murine craniofacial morphology. Univariate statistical analysis showed that Br crania were significantly smaller for all measurements as compared with the C3H/HeJ specimens. Multivariate analysis revealed that the pattern of measurement covariation differed significantly between the two samples. Results indicated that the midface was significantly shorter in length relative to the calvaria in mutant mice was compared with C3H/HeJ mice. Therefore, the sagittal midfacial growth trajectory is deficient in Br mice.

Asunto(s)

Huesos Faciales/anomalías , Ratones Mutantes/anomalías , Cráneo/anomalías , Animales , Huesos Faciales/fisiología , Femenino , Masculino , Ratones , Ratones Endogámicos C3H , Cráneo/fisiología , Soporte de Peso

RESUMEN

It has been reported that mouse pups bearing a newly identified mutation, eyelids open at birth (eob), as a homozygous condition often die within 7 days after birth although they have no external malformations other than open eyelids. We sought to determine what factors influence the viability of eob pups by performing a cross-fostering experiment using NC and NC-eob mice which are co-isogenic with each other. Viability indices of NC pups during days 0 to 7 of lactation were approximately 95% or more when they were fostered by either NC or eob mothers. However, the viability indices of eob pups were reduced to 87.3% and 36.7% when they were fostered by NC and eob mothers, respectively. Body weight gains of both NC and eob pups were slightly inhibited during the entire lactation period when they were fostered by eob mothers. In a second experiment, eob mothers were examined for milk-yielding capability and the fetuses examined for the presence of congenital visceral and skeletal malformations. Neither decreased amounts of suckled milk nor malformations were observed. Based on these results, we concluded that a remarkably high mortality of eob pups would be caused only when weak lethal factors in eob pups were combined with the slightly depressed pup-rearing capability in eob mothers.

Asunto(s)

Párpados/anomalías , Ratones Mutantes/fisiología , Animales , Párpados/embriología , Femenino , Feto/anomalías , Lactancia , Masculino , Ratones , Ratones Mutantes/anomalías , Ratones Mutantes/embriología , Embarazo , Reproducción , Tasa de Supervivencia

Asunto(s)

Anomalías del Ojo/genética , Ratones Mutantes/genética , Sindactilia/genética , Animales , Anomalías del Ojo/patología , Humanos , Ratones , Ratones Mutantes/anomalías , Síndrome