PHENOTYPIC VARIABILITY AND INCOMPLETE PENETRANCE OF SPONTANEOUS FRACTURES IN AN INBRED STRAIN OF TRANSGENIC MICE EXPRESSING A MUTATED COLLAGEN GENE (COL1A1)
R. Pereira et al., PHENOTYPIC VARIABILITY AND INCOMPLETE PENETRANCE OF SPONTANEOUS FRACTURES IN AN INBRED STRAIN OF TRANSGENIC MICE EXPRESSING A MUTATED COLLAGEN GENE (COL1A1), The Journal of clinical investigation, 93(4), 1994, pp. 1765-1769
Phenotype variability and incomplete penetrance are frequently observe
d in human monogenic diseases such as osteogenesis imperfecta. Here an
inbred strain of transgenic mice expressing an internally deleted gen
e for the pro alpha 1(I) chain of type I procollagen (COL1A1) was bred
to mild type mice of the same strain so that the inheritance of a fra
cture phenotype could be examined in a homogeneous genetic background.
To minimize the effects of environmental factors, the phenotype was e
valuated in embryos that were removed from impregnated females 1 d bef
ore term. Examination of stained skeletons from 51 transgenic embryos
from 11 separate litters demonstrated that similar to 22% had a severe
phenotype with extensive fractures of both long bones and ribs, simil
ar to 51% had a mild phenotype with fractures of ribs only, and simila
r to 27% had no fractures. The ratio of steady-state levels of the mRN
A from the transgene to the level of mRNA from the endogenous gene was
the same in all transgenic embryos. The results demonstrated that the
phenotypic variability and incomplete penetrance were not explained b
y variations in genetic background or levels in gene expression. Inste
ad, they suggested that phenotypic variation is an inherent feature of
expression of a mutated collagen gene.