FINE GENETIC-MAPPING OF THE HYP MUTATION ON MOUSE CHROMOSOME X

The hypophosphatemic (Hyp) mouse is the murine homolog of hypophosphat emic vitamin-D-resistant rickets (HYP) in human. Despite extensive inv estigations in the Hyp mouse, the pathophysiology of this X-linked dom inant disorder remains unclear. As a first step toward cloning the Hyp gene, we have generated a high-resolution linkage map in the vicinity of the Hyp locus using two independent backcross panels segregating t he Hyp mutation, one generated from an interspecific mating between C5 7BL/6J-Hyp/Hyp and Mus spretus and the other from an intrasubspecific mating between C57BL/6J-Hyp/Hyp and Mus musculus castaneus. Linkage an alyses in 1101 backcross progeny using a total of 23 DNA markers favor the following gene order from the centromere: DXMit13-(DXMit11, DXMit 34)-(DXMit36, Alas2)-(Hyp, DXMit80)-DXMit98-(DXMit28, DXMit33, DXMit70 )-Pdha1-DXMit20. This study has localized Hyp to a region of approxima tely 1 cM flanked by the proximal markers DXMit36 and Alas2 and the di stal marker DXMit98. One microsatellite marker, DXMit80 was found to b e very tightly linked to Hyp, as it was nonrecombinant with Hyp among all the progeny of both backcrosses corresponding to 1101 meioses. (C) 1996 Academic Press, Inc.