Most F
1-
Dh/+ male mice resulting from a cross between inbred DDD strain females and DH-
Dh/+ strain males exhibit growth retardation and die during the neonatal period. The lethality is caused by a combination of three independent gene loci, namely the
Dh locus on chromosome 1,
Grdhq1 locus on the X chromosome, and a putative Y chromosome-linked locus in some strains. Among these loci,
Grdhq1 was previously mapped to a distal region of the X chromosome using progeny from♀(♀DDD × ♂DH-+/+) F
1 × ♂DH-
Dh/+ mice. In this study, fine mapping of
Grdhq1 was performed using progeny of ♀(♀DDD × ♂CAST/EiJ) F
1 ♂DH-
Dh/+ mice. Contrary to expectation,
Dh/+ male pups carrying the DDD allele at
DXMit135 (genetic marker nearest to
Grdhq1) survived to weaning. The presence of modifier loci that suppressed the lethality by impeding the action of
Grdhq1 was suggested; therefore, a genome-wide scan was performed in the surviving
Dh/+ males. As a result, a significant modifier locus was identified on proximal chromosome 11. This in turn suggested that
Grdhq1 was located more distally than we had expected; that is, the actual location of
Grdhq1 appeared to be near and/or distal to the
Mid1 locus. Thus, the results revealed that the neonatal lethality in (DDD × DH-
Dh/+) F
1-
Dh/+ males was caused by the fourth gene locus on chromosome 11 in addition to the above-mentioned three gene loci on chromosomes 1, X, and Y.
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