McKusick-Kaufman syndrome (MKS) is an autosomal recessive disorder characterized 
by post-axial polydactyly, congenital heart defects and hydrometrocolpos, a 
congenital structural abnormality of female genitalia. Mutations in the MKKS 
gene have also been shown to cause some cases of Bardet-Biedl syndrome (BBS) 
which is characterized by obesity, pigmentary retinopathy, polydactyly, renal 
abnormalities and hypogenitalism with secondary features of hypertension and 
diabetes. Although there is overlap in clinical features between MKS and BBS, 
MKS patients are not obese and do not develop retinopathy or have learning 
disabilities. To further explore the pathophysiology of BBS and the related 
disorder MKS, we have developed an Mkks(-/-) mouse model. This model shows that 
the absence of Mkks leads to retinal degeneration through apoptosis, failure of 
spermatozoa flagella formation, elevated blood pressure and obesity. The obesity 
is associated with hyperphagia and decreased activity. In addition, neurological 
screening reveals deficits in olfaction and social dominance. The mice do not 
have polydactyly or vaginal abnormalities. The phenotype of the Mkks(-/-) mice 
closely resembles the phenotype of other mouse models of BBS (Bbs2(-/-) and 
Bbs4(-/-)). These observations suggest that the complete absence of MKKS leads 
to BBS while the MKS phenotype is likely to be due to specific mutations.