A knockin mouse model of the Bardet Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity.

A knockin mouse model of the Bardet Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. Research Abstract Details 

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A knockin mouse model of the Bardet Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. Abstract Text:

Roger E Davis,Ruth E Swiderski,Kamal Rahmouni,Darryl Y Nishimura,Robert F Mullins,Khristofor Agassandian,Alisdair R Philp,Charles C Searby,Michael P Andrews,Stewart Thompson,Christopher J Berry,Daniel R Thedens,Baoli Yang,Robert M Weiss,Martin D Cassell,Edwin M Stone,Val C Sheffield,Roger E Davis,Ruth E Swiderski,Kamal Rahmouni,Darryl Y Nishimura,Robert F Mullins,Khristofor Agassandian,Alisdair R Philp,Charles C Searby,Michael P Andrews,Stewart Thompson,Christopher J Berry,Daniel R Thedens,Baoli Yang,Robert M Weiss,Martin D Cassell,Edwin M Stone,Val C Sheffield,Roger E Davis,Ruth E Swiderski,Kamal Rahmouni,Darryl Y Nishimura,Robert F Mullins,Khristofor Agassandian,Alisdair R Philp,Charles C Searby,Michael P Andrews,Stewart Thompson,Christopher J Berry,Daniel R Thedens,Baoli Yang,Robert M Weiss,Martin D Cassell,Edwin M Stone,Val C Sheffield,

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder that results in retinal degeneration, obesity, cognitive impairment, polydactyly, renal abnormalities, and hypogenitalism. Of the 12 known BBS genes, BBS1 is the most commonly mutated, and a single missense mutation (M390R) accounts for approximately 80% of BBS1 cases. To gain insight into the function of BBS1, we generated a Bbs1(M390R/M390R) knockin mouse model. Mice homozygous for the M390R mutation recapitulated aspects of the human phenotype, including retinal degeneration, male infertility, and obesity. The obese mutant mice were hyperphagic and hyperleptinemic and exhibited reduced locomotor activity but no elevation in mean arterial blood pressure. Morphological evaluation of Bbs1 mutant brain neuroanatomy revealed ventriculomegaly of the lateral and third ventricles, thinning of the cerebral cortex, and reduced volume of the corpus striatum and hippocampus. Similar abnormalities were also observed in the brains of Bbs2(-/-), Bbs4(-/-), and Bbs6(-/-) mice, establishing these neuroanatomical defects as a previously undescribed BBS mouse model phenotype. Ultrastructural examination of the ependymal cell cilia that line the enlarged third ventricle of the Bbs1 mutant brains showed that, whereas the 9 + 2 arrangement of axonemal microtubules was intact, elongated cilia and cilia with abnormally swollen distal ends were present. Together with data from transmission electron microscopy analysis of photoreceptor cell connecting cilia, the Bbs1 M390R mutation does not affect axonemal structure, but it may play a role in the regulation of cilia assembly and/or function.

A knockin mouse model of the Bardet Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. Publishing Authors By Initials

RE Davis,RE Swiderski,K Rahmouni,DY Nishimura,RF Mullins,K Agassandian,AR Philp,CC Searby,MP Andrews,S Thompson,CJ Berry,DR Thedens,B Yang,RM Weiss,MD Cassell,EM Stone,VC Sheffield,RE Davis,RE Swiderski,K Rahmouni,DY Nishimura,RF Mullins,K Agassandian,AR Philp,CC Searby,MP Andrews,S Thompson,CJ Berry,DR Thedens,B Yang,RM Weiss,MD Cassell,EM Stone,VC Sheffield,RE Davis,RE Swiderski,K Rahmouni,DY Nishimura,RF Mullins,K Agassandian,AR Philp,CC Searby,MP Andrews,S Thompson,CJ Berry,DR Thedens,B Yang,RM Weiss,MD Cassell,EM Stone,VC Sheffield,

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A knockin mouse model of the Bardet Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 19422-7

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 1091-6490

DAY: 21

MONTH: 11

YEAR: 2007

A knockin mouse model of the Bardet Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for A knockin mouse model of the Bardet Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity.

AFFILIATION: Departments of Pediatrics, Internal Medicine, Ophthalmology and Visual Sciences, Anatomy and Cell Biology, Radiology, and **Obstetrics and Gynecology, and Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242.

Country: United States

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MEDLINETA: Proc Natl Acad Sci U S A

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