Retrotransposon insertion in the T-cell acute lymphocytic leukemia 1 (Tal1) gene is associated with severe renal disease and patchy alopecia in Hairpatches (Hpt) mice
| Autor: | Melissa L. Cox, Gregory A. Cox, Kenneth R. Johnson, Vishnu Hosur, Bonnie L. Lyons, Anoop Kavirayani, Rebecca L. Riding, Lisa M. Burzenski, Kimberly A. Martin, Lynn Alley, Leonard D. Shultz |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Heredity
Time Factors Mouse Genetic Linkage Gene Expression lcsh:Medicine Telangiectases Mice 0302 clinical medicine Basic Helix-Loop-Helix Transcription Factors lcsh:Science T-Cell Acute Lymphocytic Leukemia Protein 1 Regulation of gene expression 0303 health sciences Kidney Multidisciplinary Chromosome Mapping Glomerulonephritis Animal Models Up-Regulation Phenotypes medicine.anatomical_structure 030220 oncology & carcinogenesis Female Kidney Diseases Research Article Histology Genotypes Biology Real-Time Polymerase Chain Reaction Molecular Genetics 03 medical and health sciences Model Organisms Proto-Oncogene Proteins Acute lymphocytic leukemia Genetics medicine Animals Gene Regulation Crosses Genetic 030304 developmental biology lcsh:R Alopecia medicine.disease Molecular biology Disease Models Animal Gene Expression Regulation Mutation DNA Transposable Elements Intracisternal A-Particle lcsh:Q Gene Function Animal Genetics Developmental Biology Transcription Factors TAL1 |
| Zdroj: | PLoS ONE, Vol 8, Iss 1, p e53426 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | "Hairpatches" (Hpt) is a naturally occurring, autosomal semi-dominant mouse mutation. Hpt/Hpt homozygotes die in utero, while Hpt/+ heterozygotes exhibit progressive renal failure accompanied by patchy alopecia. This mutation is a model for the rare human disorder "glomerulonephritis with sparse hair and telangiectases" (OMIM 137940). Fine mapping localized the Hpt locus to a 6.7 Mb region of Chromosome 4 containing 62 known genes. Quantitative real time PCR revealed differential expression for only one gene in the interval, T-cell acute lymphocytic leukemia 1 (Tal1), which was highly upregulated in the kidney and skin of Hpt/+ mice. Southern blot analysis of Hpt mutant DNA indicated a new EcoRI site in the Tal1 gene. High throughput sequencing identified an endogenous retroviral class II intracisternal A particle insertion in Tal1 intron 4. Our data suggests that the IAP insertion in Tal1 underlies the histopathological changes in the kidney by three weeks of age, and that glomerulosclerosis is a consequence of an initial developmental defect, progressing in severity over time. The Hairpatches mouse model allows an investigation into the effects of Tal1, a transcription factor characterized by complex regulation patterns, and its effects on renal disease. |
| Databáze: | OpenAIRE |
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