Hairpatches, a single gene mutation characterized by progressive renal disease and alopecia in the mouse. A potential model for a newly described heritable human disorder.
A new murine mutation, hairpatches (Hpt), is on chromosome 4, 18.1 recombination units distal to brown near the interferon alpha and beta chain structural gene complex. On the inbred HPT/Le strain background, Hpt is semi-dominant, and Hpt/Hpt mice die in utero by 6 to 8 days of gestation. Such death in utero is associated with abnormalities of embryonic ectodermal derivatives. However on the (C57BL/6J x C3HeB/FeJ-a/a) segregating hybrid background, Hpt is a fully dominant mutation. HPT/Le Hpt/+ mice can be recognized by 3 to 4 days of age by patches of lightly pigmented skin. These mice show reduced numbers of hair follicles, abnormalities in hair follicle structure, and patchy absence of hair throughout life. By 2 weeks of age, abnormal hair follicle development is accompanied by thickening of the epidermis, reduction in levels of subcutaneous fat, and dermal inflammation. Progressive glomerulosclerosis, resulting in chronic kidney failure, is accompanied by increases in glomerular mesangial matrix, deposition of immune complexes, and glomerular enlargement. Scanning electron microscopic studies revealed abnormalities of podocytes including disorganization, swelling, and fusion of the foot processes. Increase in serum blood urea nitrogen levels accompanies conspicuous renal histopathologic changes. Cardiovascular changes in Hpt/+ mice are evidenced by hypertrophy of the left heart ventricle. Increased systolic blood pressure in these animals was found by 3 months of age. Anemia occurs in Hpt/+ mice by 40 weeks. The Hpt/+ mutation provides a valuable new animal model for chronic kidney disease accompanied by skin abnormalities and ventricular hypertrophy. The pathologic changes caused by this mutation are similar to those reported in affected family members with a newly described autosomal dominant human disease.
Shultz
L D
LD
Jackson Laboratory, Bar Harbor, Maine.
Lane
P W
PW
Coman
D R
DR
Taylor
S
S
Hall
E
E
Lyons
B
B
Wood
B G
BG
Schlager
G
G
D000505:Alopecia / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001772:Blood Cell Count; D001794:Blood Pressure; D006332:Cardiomegaly / Q000235:genetics / Q000662:veterinary; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D005796:Genes; D006824:Hybridization, Genetic; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains / Q000235:genetics*; D008855:Microscopy, Electron, Scanning