Faculty Collaboration Database

Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome. Hum Mol Genet 2005 May 01;14(9):1109-18

Date

03/18/2005

Pubmed ID

15772095

DOI

10.1093/hmg/ddi123

Scopus ID

2-s2.0-20944445215 (requires institutional sign-in at Scopus site)   164 Citations

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.

Author List

Fath MA, Mullins RF, Searby C, Nishimura DY, Wei J, Rahmouni K, Davis RE, Tayeh MK, Andrews M, Yang B, Sigmund CD, Stone EM, Sheffield VC

Author

Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Abnormalities, Multiple
Alleles
Animals
Bardet-Biedl Syndrome
Blood Pressure
Disease Models, Animal
Genes, Recessive
Humans
Leptin
Male
Mice
Mice, Knockout
Models, Genetic
Obesity
Phenotype
Proteins
Retinal Degeneration
Social Dominance
Sperm Tail
Syndrome