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 (Mi(or)) mutation are white, microphthalmic animals with retarded incisor development. To investigate whether this mutation causes osteopetrosis, we examined skeletal tissues of the Mi(or) mouse. A typical osteopetrotic lesion, accumulation of unresorbed primary spongiosa, was found at the metaphyses of long bones and at the costochondral junctions in Mi(or)/Mi(or) 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 Mi(or)/Mi(or) mice increased progressively during the first 5 weeks after birth. However, adult Mi(or)/Mi(or) mice 3 months or older showed improvement of the osteopetrotic condition, although the disease was not completely resolved. Ultrastructurally, osteoclasts of Mi(or)/Mi(or) mice had well developed ruffled borders. These results show that the Mi(or) 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 Mi(or) phenotype resembles the intermediate autosomal recessive osteopetrosis in humans.
|Original language||English (US)|
|Number of pages||12|
|Journal||American Journal of Pathology|
|State||Published - Jan 1 1995|
ASJC Scopus subject areas
- Pathology and Forensic Medicine