title: Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome.
abstract: 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.
authors.affiliation: Department of Pediatrics, Division of Medcal Genetics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Fath
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Charles
authors.initials: C
authors.lastname: Searby
authors.forename: Darryl Y
authors.initials: DY
authors.lastname: Nishimura
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.forename: Roger E
authors.initials: RE
authors.lastname: Davis
authors.forename: Marwan K
authors.initials: MK
authors.lastname: Tayeh
authors.forename: Michael
authors.initials: M
authors.lastname: Andrews
authors.forename: Baoli
authors.initials: B
authors.lastname: Yang
authors.forename: Curt D
authors.initials: CD
authors.lastname: Sigmund
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000483:Alleles; D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000235:genetics; D004195:Disease Models, Animal; D005808:Genes, Recessive; D006801:Humans; D020738:Leptin / Q000097:blood / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology; D012930:Social Dominance; D013082:Sperm Tail / Q000378:metabolism / Q000473:pathology; D013577:Syndrome
chemical_list: D020738:Leptin; D011506:Proteins