Effects of the sex-linked prenatal lethal gene tortoise (Moto) on reproduction and growth in the mouse.

The sex-linked prenatally lethal gene tortoise (Moto), an animal model for the human disorder known as Menkes' Kinky Hair Syndrome (MKHS), was studied in the mouse (Mus musculus). The genetic effects upon reproductive performance, birth weight, preweaning growth, and mortality were evaluated to characterize the debilitating effects of the disorder. Reproductive performance of mice were evaluated in two mating types (dam X sire), mutant female (To/+) X normal male (+/Y) and normal female (+/+) X normal male (+/Y). Litter size was reduced in the To/+ X +/Y mating type as expected due to the death of To/Y offspring in utero. Adjusted birth weight of To/+ and +/Y offspring were identical, and both were greater (P less than 0.05) than +/+ offspring. Within one day, however, the To/+ littermates were smaller (P less than 0.05) than +/+ and +/Y and remained consistently inferior in growth through day 30. Normal females and normal males were similar (P greater than 0.05) in growth from day 1 through day 21. Thereafter, +/Y mice were consistently heavier (P less than 0.05) than +/+ mice through day 30. The To/+ genotype had the greatest (13.8%) preweaning mortality rate; +/+ and +/Y genotypes were comparable as were overall comparisons between parity 1 and 2. It is apparent from this study that the copper deficiency and lethality occurring in the progeny of mottled mice were primarily the result of the gene actions in the heterozygote animals. Progression of the disorder may be prevented by experimental determination of both the timing and targeting of in utero therapy in mottled mice and MKHS fetuses.