C3Fe;B6-Tal1^Hpt/J

Stock number: 021505
Research areas: Dermatology Research, Developmental Biology Research, Internal/Organ Research

Description

Hpt mice contain a spontaneous mutation which results in an endogenous retroviral class II intracisternal A particle (IAP) insertion in intron 4 of the T-cell acute lymphocytic leukemia 1 (Tal1) gene. These mice are useful for studying glomerulonephritis and alopecia.

Detailed description

Mice heterozygous for this spontaneous mutation, Hpt, are viable and fertile, while homozygotes die in utero. These mice contain an endogenous retroviral class II intracisternal A particle (IAP) insertion in intron 4 of the T-cell acute lymphocytic leukemia 1 (Tal1) gene. IAPs are transposable elements that induce mutations and cell transformation by disrupting gene expression. Tal1 is a transcription factor expressed throughout development which regulates hematopoietic, neural, and endothelial precursor expression. Tal1 is also expressed during mammalian renal development. Zebrafish models of Tal1 overexpression display a reduction in endothelial progenitor cells destined for the kidney and skin, and also disruption of vasculogenesis in these organs. These Hpt mice overexpress Tal1 in kidney and skin, and exhibit progressive renal failure accompanied by patchy alopecia. Hpt/+ mice older than one year have significantly lower hemoglobin levels and hematocrit readings compared with wildtype controls. They exhibit a progressive decline in renal function with elevated blood urea nitrogen (BUN) values. These aged Hpt/+ mice exhibit diffuse and nodular mesangial matrix expansion with mesangiolysis and capillary aneurysms in glomeruli, and thickening of glomerular and capsular basement membranes. This mutation is a model for the human disorder "glomerulonephritis with sparse hair and telangiectases".

Development

The Mouse Mutant Stock Center of The Jackson Laboratory identified a novel spontaneous mutation causing skin abnormalities and progressive renal disease. The mutation, named "Hairpatches" (Hpt), was found in a segregating hybrid stock of B6C3Fe-a/a mice carrying the nonagouti allele (a) from C57BL/6J. Using a fine mapping approach, the Hpt locus was mapped to a 6.7 Mb region of Chromosome 4 containing 62 known genes. Quantitative real time PCR revealed differential expression of one gene in the interval, T-cell acute lymphocytic leukemia 1 (Tal1), which was highly expressed in kidney and skin. Sequencing of Tal1 identified an endogenous retroviral class II intracisternal A particle (IAP) insertion in intron 4. IAPs are transposable elements that induce mutations and cell transformation by disrupting gene expression. Hpt mice have been maintained by sibling matings for at least 50 generations.

Allele

Symbol: Tal1^Hpt
Name: hair patches
MGI accession ID: MGI:1859843
Generation method: Spontaneous
Synonyms: Hpa
Marker symbol: Tal1
Marker name: T cell acute lymphocytic leukemia 1
Chromosome: 4
Strain of origin: (C57BL/6J x C3FeLe.B6-a/a)F1
Molecular note: An endogenous retroviral class II intracisternal A particle (IAP) inserted into intron 4. Quantitative real time PCR revealed differential expression of one gene in the interval, T-cell acute lymphocytic leukemia 1 (Tal1), which was highly expressed in kidney and skin.