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-link ed Opitz G/BBB syndrome, a defect of midline development, MIDI is loca ted on the distal short arm of the human X chromosome (Xp22.3) and enc odes a novel member of the B box family of zinc finger proteins, We ha ve now cloned the murine homolog of MIDI and performed preliminary exp ression studies during development, Midi expression in undifferentiate d cells in the central nervous, gastrointestinal and urogenital system s suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome, We have also fo und that Midi is located within the mouse pseudoautosomal region (PAR) in Mus musculus, while it seems to be X-specific in Mus spretus, Ther efore, Midi is likely to be a recent acquisition of the M. musculus PA R, Genetic and FISH analyses also demonstrated a high frequency of une qual crossovers in the murine PAR, creating spontaneous deletion/dupli cation events involving Midi. These data provide evidence for the firs t time that genetic instability of the PAR may affect functionally imp ortant genes, In addition, we show that MIDI is the first example of a gene subject to X-inactivation in man while escaping it in mouse, The se data contribute to a better understanding of the molecular content and evolution of the rodent PAR.