Parental origin of mutant allele does not explain absence of gene dose in X-linked Hyp mice.

The expectation for a gene dose effect in an X-linked phenotype is that the corresponding metrical trait in heterozygous females will lie between values for affected hemizygous males and unaffected males and females. We made sequential measurements (at 30, 60, 90, 120 and 150 days) of serum phosphate concentration and tail length in mice with X-linked hypophosphatemia (genotypes: Hyp/Y, Hyp/+ and Hyp/Hyp) and in their normal litter-mates (genotypes: +/Y, +/+). We also measured renal mitochondrial 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) activity in 5 to 7-month-old mice fed control and low phosphate diets and representing all five genotypes. The animals were obtained by controlled breeding under uniform environmental conditions. The mutant animals all had uniformly and significantly lower serum phosphate levels, shorter tail length and higher 24-hydroxylase activity relative to unaffected litter-mates. There was no evidence of a gene dose effect because values were not significantly different among the three mutant genotypes. We also studied the influence of gamete of origin on serum phosphate, tail length and renal mitochondrial 24-hydroxylase activity in the Hyp/+ offspring of affected males (Hyp/Y) or affected females (Hyp/+ or Hyp/Hyp). We found no effect on the distribution of trait values. We conclude that parental origin of mutant allele does not explain the absence of a gene dose effect in Hyp mice.