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Dominant lethality of the mouse skeletal mutation tail-short (Ts) is determined by the Ts allele from mating partners
J Ishijima1, H Yasui, M Morishima
1Mammalian Genetics Laboratory, National Institute of Genetics, Shizuoka-ken, Japan.
Abstract:
Mice with the Tail-short (Ts) mutation have a short, kinky tail and numerous skeletal abnormalities, including a homeotic anteroposterior patterning problem involving the axial skeleton. The viability of Ts heterozygotes varies dramatically, depending on the mouse strain crossed with the mutant strain. At the extremes, the heterozygotes are viable or lethal prenatally. In this study, we found that laboratory mouse strains could be divided into two groups. A cross with strains from the first group yielded viable Ts heterozygotes, whereas a cross with the second group resulted in dominant lethality in utero. We planned to map the gene(s) that controls strain differences in the viability of the Ts heterozygotes. The result clearly indicated that a single chromosomal region, genetically inseparable from the Ts locus, is responsible for these differences. This suggests that allelism at the Ts locus generates variable manifestation of the mutant phenotype. Morphological and histological analyses indicated that embryos from the lethal cross exhibit severe developmental defects from the gastrulation stage through the early fetal stage. In particular, the umbilical vein does not develop properly. All of these results suggest that the phenotype of the Ts mutant is modified by the Ts alleles of the mating partners.
Insights
The Tail-short (Ts) mutation in mice causes skeletal issues. Genetic factors in different mouse strains significantly influence the viability of Ts heterozygotes, leading to either survival or prenatal lethality.
Area of Science:
- Developmental biology
- Genetics
- Skeletal biology
Background:
- The Tail-short (Ts) mutation in mice presents with a short, kinky tail and significant skeletal abnormalities, including axial skeleton patterning defects.
- The viability of Ts heterozygotes is highly variable and dependent on the genetic background of the mouse strain used in crosses.
Purpose of the Study:
- To identify the genetic factors responsible for the strain-dependent viability differences observed in Ts heterozygotes.
- To investigate the underlying developmental mechanisms contributing to the variable manifestation of the Ts mutant phenotype.
Main Methods:
- Genetic mapping to identify the chromosomal region controlling viability.
- Comparative morphological and histological analyses of embryos from viable and lethal crosses.
Main Results:
- Laboratory mouse strains were categorized into two groups based on their effect on Ts heterozygote viability: one group yielding viable offspring, the other resulting in dominant prenatal lethality.
- Genetic mapping revealed a single chromosomal region, tightly linked to the Ts locus, responsible for these viability differences.
- Embryos from lethal crosses displayed severe developmental defects, notably improper umbilical vein development, from gastrulation through early fetal stages.
Conclusions:
- The strain-specific differences in Ts heterozygote viability are controlled by genetic factors linked to the Ts locus.
- Allelic interactions at the Ts locus play a critical role in modulating the severity and outcome of the Ts mutant phenotype.
- Proper umbilical vein development is crucial for the survival of Ts heterozygotes, and its disruption is linked to the lethal phenotype.