Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin

Darryl Y. Nishimura, Melissa Fath, Robert F. Mullins, Charles Searby, Michael Andrews, Roger Davis, Jeaneen L. Andorf, Kirk Mykytyn, Ruth E. Swiderski, Baoli Yang, Rivka Carmi, Edwin M. Stone, Val C. Sheffield

Research output: Contribution to journalArticlepeer-review

286 Scopus citations

Abstract

Bardet-Biedl syndrome (BBS) is a heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, hypogenitalism, and an increased incidence of diabetes and hypertension. No information is available regarding the specific function of BBS2. We show that mice lacking Bbs2 gene expression have major components of the human phenotype, including obesity and retinopathy. In addition, these mice have phenotypes associated with cilia dysfunction, including retinopathy, renal cysts, male infertility, and a deficit in olfaction. With the exception of male infertility, these phenotypes are not caused by a complete absence of cilia. We demonstrate that BBS2 retinopathy involves normal retina development followed by apoptotic death of photoreceptors, the primary ciliated cells of the retina. Photoreceptor cell death is preceded by mislocalization of rhodopsin, indicating a defect in transport. We also demonstrate that Bbs2-/- mice and a second BBS mouse model, Bbs4-/-, have a defect in social function. The evaluation of Bbs2-/- mice indicates additional phenotypes that should be evaluated in human patients, including deficits in social interaction and infertility.

Original languageEnglish
Pages (from-to)16588-16593
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number47
DOIs
StatePublished - 23 Nov 2004

Keywords

  • Bardet-Biedl syndrome
  • Mouse model
  • Obesity

Fingerprint

Dive into the research topics of 'Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin'. Together they form a unique fingerprint.

Cite this