The dactylaplasia foot phenotype was first observed in a female mouse at generation F20 of an incipient congenic strain; this strain was derived from an initial cross of SM/Ckc x LG/Ckc mice followed by 7 generations of backcrossing to SM/Ckc. Inheritance of the Fbxw4Dac phenotype on this background was shown to be autosomal semidominant, heterozygotes having reduced numbers of phalanges and homozygotes dying perinatally (Chai 1981).
Outcrossing to mice of various inbred strains revealed the existence of a second, unlinked gene whose dominant form, Mdac, suppresses the Fbxw4Dac phenotype (Chai 1981).
An intercross among (SM/Ckc-Fbxw4Dac x NZB/B1NJ)F1 mice, performed to map Fbxw4Dac and the modifier locus, mdac (for which NZB, like SM, carries the permissive, recessive allele), unexpectedly yielded Fbxw4Dac homozygotes. The phenotype of these mice was more severe than on the SM background, as they had only one digit on each foot. However, they proved to be fully viable and fertile (Johnson et al. 1995). A doubly homozygous (Fbxw4Dac/Fbxw4Dac mdac/mdac) stock was developed from these animals and has been maintained by sib inbreeding for more than 35 generations, so that SMNZB-Fbxw4Dac is now an inbred strain.
|Gene Symbol and Name||Fbxw4, F-box and WD-40 domain protein 4|
|Strain of Origin||SM/Ckc|
|Molecular Note||This mutation is a MusD family transposon insertion of 7486 nucleotides located approximately 10 kb upstream of exon A.|