title: Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly.
abstract: The functions of the proteins encoded by the Bardet-Biedl syndrome (BBS) genes are unknown. Mutations in these genes lead to the pleiotropic human disorder BBS, which is characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Secondary features include diabetes mellitus and hypertension. Recently, it has been suggested that the BBS phenotypes are the result of a lack of cilia formation or function. In this study, we show that mice lacking the Bbs4 protein have major components of the human phenotype, including obesity and retinal degeneration. We show that Bbs4-null mice develop both motile and primary cilia, demonstrating that Bbs4 is not required for global cilia formation. Interestingly, male Bbs4-null mice do not form spermatozoa flagella, and BBS4 retinopathy involves apoptotic death of photoreceptors, the primary ciliated cells of the retina. These mutation data demonstrate a connection between the function of a BBS protein and cilia. To further evaluate an association between cilia and BBS, we performed homology comparisons of BBS proteins in model organisms and find that BBS proteins are specifically conserved in ciliated organisms.
authors.affiliation: Department of Pharmacology and Division of Human Genetics, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Kirk
authors.initials: K
authors.lastname: Mykytyn
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Michael
authors.initials: M
authors.lastname: Andrews
authors.forename: Annie P
authors.initials: AP
authors.lastname: Chiang
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Swiderski
authors.forename: Baoli
authors.initials: B
authors.lastname: Yang
authors.forename: Terry
authors.initials: T
authors.lastname: Braun
authors.forename: Thomas
authors.initials: T
authors.lastname: Casavant
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D000818:Animals; D017209:Apoptosis; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D002923:Cilia / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics; D005260:Female; D005407:Flagella / Q000378:metabolism* / Q000473:pathology; D018390:Gene Targeting; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D010802:Phylogeny; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology
chemical_list: C429655:BBS4 protein, human; D008869:Microtubule-Associated Proteins; D011506:Proteins; D004247:DNA