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.
Document Type
Article
Publication Date
2013
JAX Source
PLoS One 2013; 8(1):e53426.
Volume
8
Issue
1
First Page
53426
Last Page
53426
ISSN
1932-6203
PMID
23301070
Abstract
"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. PLoS One 2013; 8(1):e53426.
Recommended Citation
Hosur V,
Cox M,
Burzenski L,
Alley L,
Lyons BL,
Kavirayani A,
Martin K,
Cox GA,
Johnson KR,
Riding R,
Shultz LD.
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. PLoS One 2013; 8(1):e53426.