RESUMEN
Transgenic mice expressing the Notch 4 intracellular domain (ICD) (Int3) in the mammary gland have two phenotypes: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. We have conditionally ablated the Rbpj gene in the mammary glands of mice expressing whey acidic protein (Wap)-Int3. Interestingly, Rbpj knockout mice (Wap-Cre(+)/Rbpj(-/-)/Wap-Int3) have normal mammary gland development, suggesting that the effect of endogenous Notch signaling on mammary gland development is complete by day 15 of pregnancy. RBP-J heterozygous (Wap-Cre(+)/Rbpj(-/+)/Wap-Int3) and Rbpj control (Rbpj(flox/flox)/Wap-Int3) mice are phenotypically the same as Wap-Int3 mice with respect to mammary gland development and tumorigenesis. In addition, the Wap-Cre(+)/Rbpj(-/-)/Wap-Int3-knockout mice also developed mammary tumors at a frequency similar to Rbpj heterozygous and Wap-Int3 control mice but with a slightly longer latency. Thus, the effect on mammary gland development is dependent on the interaction of the Notch ICD with the transcription repressor/activator Rbpj, and Notch-induced mammary tumor development is independent of this interaction.
Asunto(s)
Glándulas Mamarias Animales/embriología , Neoplasias Mamarias Experimentales/genética , Proteínas de Neoplasias/fisiología , Proteínas Proto-Oncogénicas/fisiología , Receptores Notch/fisiología , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/patología , Agar , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Ciclo Celular/metabolismo , Transformación Celular Viral/genética , Femenino , Proteínas de Homeodominio/metabolismo , Neoplasias Mamarias Experimentales/patología , Virus del Tumor Mamario del Ratón/genética , Ratones , Ratones Noqueados , Ratones Desnudos , Proteínas de la Leche/genética , Proteínas de Neoplasias/genética , Embarazo , Estructura Terciaria de Proteína , Proteínas Proto-Oncogénicas/química , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/genética , Receptor Notch4 , Receptores Notch/química , Receptores Notch/deficiencia , Receptores Notch/genética , Proteínas Recombinantes de Fusión/fisiología , Proteínas Represoras/genética , Secuencias Repetidas Terminales/genética , Factor de Transcripción HES-1 , Células Tumorales Cultivadas/citologíaRESUMEN
Genes coding for growth hormone (GH) and GH receptor (GHR) are candidates for quantitative trait markers in farm animals. This work describes a search for nucleotide sequence polymorphisms within the 5'-region of the bovine GHR gene. Two new single nucleotide polymorphisms were found: restriction fragment length polymorphisms (RFLPs) at a Fnu4HI/TseI site (C/T transition at position -1104), and at a Sau96I site (C/T transition at position -262). The Fnu4HI/TseI polymorphic site is located within the 1.2-kbp LINE-1 retrotransposon upstream of the P1 promoter, while the Sau96I RFLP locates in the P1 promoter for exon 1A. The appearance of the Sau96I RFLP was studied in representatives of two bovine species, Bos taurus and Bos indicus. An absolute correlation was observed between Sau96I genotype and the insertion/deletion of LINE-1.
Asunto(s)
Cruzamiento/métodos , Bovinos/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de Somatotropina/genética , Animales , Cartilla de ADN , Elementos de Nucleótido Esparcido Largo/genética , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Secuencia de ADN , Especificidad de la EspecieRESUMEN
The object of this study was to investigate gene polymorphism in the Polish Red (PR) cattle, a local Polish breed included in the FAO conservation programme. Milk protein genes and other genes with possible effect on production traits were analysed. Frequencies of different gene variants were compared with those in the Polish Friesian cattle. The following gene polymorphisms were analysed with PCR/RFLP technique: milk protein genes--kappa-casein and beta-lactoglobulin, growth hormone (GH), PitI (a transcription factor) and leptin. Moreover, SSCP analysis was performed of myostatin (MSTN) gene at the site previously shown to cause muscle overgrowth in Belgian Blue double-muscled cattle. A significant difference was found in this study between kappa-casein A and B allele frequency in PR and Friesian cattle. No such differences were found in the frequency of A and B alleles of beta-lactoglobulin, L and V alleles of GH, A and B alleles of PitI, and A, B and C alleles of leptin gene. In the analysed group of the Polish Red cattle three animals were found with the rare AI genotype of -lactoglobulin. No such genotype was identified in analysed Friesians. Moreover, 8 PR animals were identified carrying a mutation in MSTN gene, possibly identical to that causing the double-muscled phenotype in some breeds of meat cattle.