Homozygotes fail to thrive, beginning to fall behind their littermates in size by about 2 weeks of age and not growing further after 3 weeks of age. They generally die between 3 and 5 months of age with a few living longer. They have rounded skulls, large eyes, larger than normal optic nerves, and their gait stiffens with age. Intraocular pressure measured at 1 and 2 months of age was normal.
The mutation small and bugged-eyed arose spontaneously at The Jackson Laboratory and was found in the F2 offspring of the inbred C57BL/6J strain and a targeted mutant congenic strain in which the Chromosome 17 targeted mutation had been generated in a 129P2/OlaHsd derived ES Cell and backcrossed 9 generations (N9) onto C57BL/6J. Subsequent to identifying this spontaneous mutation the targeted mutation was bred out of this mutant subline by a further backcross to C57BL/6J and intercrossing with selection against the targeted mutation. It was determined that this mutation occurred in C57BL/6J-derived sequence. In 2008 sperm was cryopreserved from males heterozygous for small and bugged-eyed.
|Allele Name||small and bugged-eyed|
|Gene Symbol and Name||Mmp14, matrix metallopeptidase 14 (membrane-inserted)|
|Strain of Origin||C57BL/6J|
|Molecular Note||A C to T transition in Chromosome 14 bapse pair 54,436,154 (GRCm38) is predicted to cause a p.R92C mutation directly adjacent to a critical cysteine in the cysteine switch regulatory domain.|