We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

BBS proteins interact genetically with the IFT pathway to influence SHH-related phenotypes.

Human molecular genetics | May 1, 2012

There are numerous genes for which loss-of-function mutations do not produce apparent phenotypes even though statistically significant quantitative changes to biological pathways are observed. To evaluate the biological meaning of small effects is challenging. Bardet-Biedl syndrome (BBS) is a heterogeneous autosomal recessive disorder characterized by obesity, retinopathy, polydactyly, renal malformations, learning disabilities and hypogenitalism, as well as secondary phenotypes including diabetes and hypertension. BBS knockout mice recapitulate most human phenotypes including obesity, retinal degeneration and male infertility. However, BBS knockout mice do not develop polydacyly. Here we showed that the loss of BBS genes in mice result in accumulation of Smoothened and Patched 1 in cilia and have a decreased Shh response. Knockout of Bbs7 combined with a hypomorphic Ift88 allele (orpk as a model for Shh dysfuction) results in embryonic lethality with e12.5 embryos having exencephaly, pericardial edema, cleft palate and abnormal limb development, phenotypes not observed in Bbs7(-/-) mice. Our results indicate that BBS genes modulate Shh pathway activity and interact genetically with the intraflagellar transport (IFT) pathway to play a role in mammalian development. This study illustrates an effective approach to appreciate the biological significance of a small effect.

Pubmed ID: 22228099 RIS Download

Mesh terms: Animals | Bardet-Biedl Syndrome | Cells, Cultured | Cilia | Female | Hedgehog Proteins | Humans | Male | Mice | Mice, Knockout | Microtubule-Associated Proteins | Mutant Proteins | Patched Receptors | Patched-1 Receptor | Phenotype | Pregnancy | Receptors, Cell Surface | Receptors, G-Protein-Coupled | Recombinant Proteins | Signal Transduction | Smoothened Receptor | Transfection | Tumor Suppressor Proteins

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NEI NIH HHS, Id: R01EY017168
  • Agency: NEI NIH HHS, Id: R01EY110298
  • Agency: Howard Hughes Medical Institute, Id:

Gene Ontology (Data, Gene Annotation)

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.