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Human Molecular Genetics Advance Access originally published online on March 16, 2005
Human Molecular Genetics 2005 14(9):1109-1118; doi:10.1093/hmg/ddi123
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Mkks-null mice have a phenotype resembling Bardet–Biedl syndrome

Melissa A. Fath1,5, Robert F. Mullins2, Charles Searby1,5, Darryl Y. Nishimura1,5, Jun Wei1,5, Kamal Rahmouni3, Roger E. Davis1, Marwan K. Tayeh1, Michael Andrews1,5, Baoli Yang4, Curt D. Sigmund3, Edwin M. Stone2,5 and Val C. Sheffield1,5,*

1Department of Pediatrics, Division of Medical Genetics, 2Department of Ophthalmology, 3Department of Internal Medicine, 4Department of Obstetrics and Gynecology and 5Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA

* To whom correspondence should be addressed at: Department of Pediatrics, Division of Medical Genetics, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA. Tel: +1 3193356898; Fax: +1 3193357588; Email: val-sheffield{at}uiowa.edu

Received January 12, 2005; Accepted March 6, 2005

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.


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