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-linked Opitz G/BBB syndrome, a defect of midline development, MIDI is located on the distal short arm of the human X chromosome (Xp22.3) and encodes a novel member of the B box family of zinc finger proteins, We have now cloned the murine homolog of MIDI and performed preliminary expression studies during development, Midi expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome, We have also found that Midi is located within the mouse pseudoautosomal region (PAR) in Mus musculus, while it seems to be X-specific in Mus spretus, Therefore, Midi is likely to be a recent acquisition of the M. musculus PAR, Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Midi. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important 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, These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.