Overview of the mouse Agouti viable yellow mutation

A -Brown Mouse -normal

B - Yellow mouse with insertion in promoter sequences

C -Chemically altered insertion causing variable phenotype

brown mouse

yellow agouti


Similarities between of the mechanism of action of the Agouti Viable Yellow Mutant and mutations in the canine COX-2 gene that cause renal dysplasia.

Disruption of DNA that controls amount of protein produced (promoter region of the gene).
Chemical modification (methylation) of promoter - applies to mutant genes only
Variable chemical modification of promoter-
applies to mutant genes only

Chemical modification during embryogenesis
applies to mutant genes only

Variable phenotype
influences during embryogenesis

Mode of inheritance
Lower amounts of protein produced-
applies to mutant genes only


Dominant with incomplete penetrance
RD alleles


Highly probable*

Dominant with incomplete penetrance

Highly probable*

Unlike the Agouti viable mouse mutant that is clearly visible kidney defects typical of this inherited form of RD can only be seen with a renal wedge biopsy. The incomplete penetrance of the Cox-2 mutant alleles leads to a highly variable range of kidney defects.  Animals with a moderate to severe defect may have no symptoms until the renal function is diminished  by 70-75%, and this can take years to develop. This is why RD is actually a late onset disease.  Most dogs with one or two copies of a RD mutant allele are sub-clinical.