The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region

We have recently reported isolation of the gene responsible for X- linkedOpitz G/BBB syndrome, a defect of midline development. MID1 is located onthe distal short arm of the human X chromosome (Xp22. 3) and encodes anovel member of the B box family of zinc finger proteins. We have nowcloned the murine homolog of MID1 and performed preliminary expressionstudies during development. Mid1 expression in undifferentiated cells inthe central nervous, gastrointestinal and urogenital systems suggests thatabnormal cell proliferation may underlie the defect in midline developmentcharacteristic of Opitz syndrome. We have also found that Mid1 is locatedwithin the mouse pseudoautosomal region (PAR) in Mus musculus , while itseems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be arecent acquisition of the M. musculus PAR. Genetic and FISH analyses alsodemonstrated a high frequency of unequal crossovers in the murine PAR,creating spontaneous deletion/duplication events involving Mid1. These dataprovide evidence for the first time that genetic instability of the PAR mayaffect functionally important genes. In addition, we show that MID1 is thefirst example of a gene subject to X-inactivation in man while escaping itin mouse. These data contribute to a better understanding of the molecularcontent and evolution of the rodent PAR.