Phenotypic characterization of Bbs4 null mice reveals age-dependent penetrance and variable expressivity.

Journal Article (Journal Article)

Bardet-Biedl syndrome (BBS) is a rare oligogenic disorder exhibiting both clinical and genetic heterogeneity. Although the BBS phenotype is variable both between and within families, the syndrome is characterized by the hallmarks of developmental and learning difficulties, post-axial polydactylia, obesity, hypogenitalism, renal abnormalities, retinal dystrophy, and several less frequently observed features. Eleven genes mutated in BBS patients have been identified, and more are expected to exist, since about 20-30% of all families cannot be explained by the known loci. To investigate the etiopathogenesis of BBS, we created a mouse null for one of the murine homologues, Bbs4, to assess the contribution of one gene to the pleiotropic murine Bbs phenotype. Bbs4 null mice, although initially runted compared to their littermates, ultimately become obese in a gender-dependent manner, females earlier and with more severity than males. Blood chemistry tests indicated abnormal lipid profiles, signs of liver dysfunction, and elevated insulin and leptin levels reminiscent of metabolic syndrome. As in patients with BBS, we found age-dependent retinal dystrophy. Behavioral assessment revealed that mutant mice displayed more anxiety-related responses and reduced social dominance. We noted the rare occurrence of birth defects, including neural tube defects and hydrometrocolpos, in the null mice. Evaluations of these null mice have uncovered phenotypic features with age-dependent penetrance and variable expressivity, partially recapitulating the human BBS phenotype.

Full Text

Duke Authors

Cited Authors

  • Eichers, ER; Abd-El-Barr, MM; Paylor, R; Lewis, RA; Bi, W; Lin, X; Meehan, TP; Stockton, DW; Wu, SM; Lindsay, E; Justice, MJ; Beales, PL; Katsanis, N; Lupski, JR

Published Date

  • September 2006

Published In

Volume / Issue

  • 120 / 2

Start / End Page

  • 211 - 226

PubMed ID

  • 16794820

International Standard Serial Number (ISSN)

  • 0340-6717

Digital Object Identifier (DOI)

  • 10.1007/s00439-006-0197-y


  • eng

Conference Location

  • Germany