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

 
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.

GENE	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	Enviornmetal influences during embryogenesis	Mode of inheritance	Lower amounts of protein produced- applies to mutant genes only
AGOUTI (Avy)	✔	✔	✔	✔	✔	✔	Dominant with incomplete penetrance	✔
COX-2 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. 


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