Multigenic Heteroygous Mutations in Bbs1/bbs7 Result in Pathogenic Phenotypes in Mice

Abstract

Purpose: : We sought to determine if pathology characteristic of Bardet-Biedl syndrome may result from multigenic interactions between Bbs1 and Bbs7 in mice.

Methods: : Mice heterozygous for both the Bbs1M390R mutation and the Bbs7 null mutation, were evaluated using: 1) histological and immunohistochemical assessment of the retina; 2) full field electroretinogram (ERG); and 3) body mass analysis. Animals homozygous for the Bbs1M390R or Bbs7 null wild type littermates were also assessed.

Results: : A significant reduction is observed in the ERG B-wave of double heterozygous animals compared to wild type and single heterozygotes. In accordance, body mass data suggests a significant increase is observed in double heterozygotes compared to single heterozygotes and wild type littermates.

Conclusions: : Double heterozygote animals for Bbs1M390R/7 (null) have abnormalities that suggest a pathology similar to Bardet-Biedl syndrome observed in homozygous knock-in or knock-out animals. This implies that patients who are heterozygous for changes in two specific BBS genes may also manifest some of the symptoms of the disease.

Keywords: electroretinography: non-clinical • retinal degenerations: hereditary • immunohistochemistry