Fine genetic mapping of the Hyp mutation on mouse chromosome X

Abstract

The hypophosphatemic (Hyp) mouse is the murine homolog of hypophosphatemic vitamin-D-resistant rickets (HYP) in human. Despite extensive investigations in the Hyp mouse, the pathophysiology of this X-linked dominant 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 the Hyp mutation, one generated from an interspecific mating between C57BL/6J-Hyp/Hyp and Mus spretus and the other from an intrasubspecific mating between C57BL/6J-Hyp/Hyp and Mus musculus castaneus. Linkage analyses in 1101 backcross progeny using a total of 23 DNA markers favor the following gene order from the centromere: DXMitl3-(DXMit11, DXMit34)-(DXMit36, Alas2)-(Hyp, DXMit8O)-DXMi198-(DXMit28, DXMit33, DXMit7O)-Pdhal-DXMit2O. This study has localized Hyp to a region of approximately 1 cM flanked by the proximal markers DXMit36 and Alas2 and the distal marker DXMit98. One microsatellite marker, DXMit8O, was found to be very tightly linked to Hyp, as it was nonrecombinant with Hyp among all the progeny of both backcrosses corresponding to 1101 meioses.