title: Mild osteopetrosis in the microphthalmia-oak ridge mouse. A model for intermediate autosomal recessive osteopetrosis in humans.
abstract: Mutations at the mouse microphthalmia (mi) locus affect coat color, eye development, and mast cells. The original allele, mi, also shows severe osteopetrosis. Mice homozygous for the microphthalmia-Oak Ridge (Mior) mutation are white, microphthalmic animals with retarded incisor development. To investigate whether this mutation causes osteopetrosis, we examined skeletal tissues of the Mior mouse. A typical osteopetrotic lesion, accumulation of unresorbed primary spongiosa, was found at the metaphyses of long bones and at the costochondral junctions in Mior/Mior mice from 10 days to 37 days of age, whereas no accumulation was seen at the mid-diaphyses in these bones. The osteopetrotic conditions of Mior/Mior mice increased progressively during the first 5 weeks after birth. However, adult Mior/Mior mice 3 months or older showed improvement of the osteopetrotic condition, although the disease was not completely resolved. Ultrastructurally, osteoclasts of Mior/Mior mice had well developed ruffled borders. These results show that the Mior mutation has milder osteopetrotic changes than the original mi mutation, a surprising observation given that both mutations affect the same functional domain of the mi protein, a basic-Helix-Loop-Helix-Zipper transcription factor. The Mior phenotype resembles the intermediate autosomal recessive osteopetrosis in humans.
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006132:Growth Plate / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010010:Osteoclasts / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology; D010022:Osteopetrosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D011859:Radiography