These ADP-ribosylation factor-like 6 (Arl6) or Bbs3 knockout mice exhibit several characteristics of Bardet-Biedl syndrome (BBS) including retinal degeneration, male infertility, severe hydrochephalus, increased body fat (but not obesity), and hypertension.
Val Sheffield, University of Iowa, HHMI
ADP-ribosylation factor-like 6 (Arl6) or Bbs3 is a small GTPase and one of 16 genes associated with Bardet-Biedl syndrome (BBS). BBS3 interacts with the 7 BBS proteins that form the BBSome complex, and is required for ciliary localization of the BBSome. Mice homozygous for this knockout mutation exhibit several characteristics of BBS including retinal degeneration, male infertility (caused by absence of sperm flagella), severe hydrochephalus, misshapen ependymal cell cilia, altered cilia beat mechanics, increased body fat (but not obesity), increased arterial pressure (hypertension) and increased heart rate. Both the C57BL/6J genetic background (see Stock No. 021215) and the C3H genetic background (see Stock No. 021217) strains show reduced viability of homozygotes, but otherwise there are no known phenotypic differences between the C57BL/6, C3H, mixed C57BL/6-129 (Stock No. 018443), and 129 (see Stock No. 021216) genetic backgrounds. This mutant mouse strain may be useful in studies of Bardet-Biedl syndrome.
The targeting vector uses a neomycin resistance gene to replace exons 6 and 7 creating a frameshift that disrupts both known mRNA isoforms. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl<+>-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred to C57BL/6J. Heterozygotes were intercrossed to generate homozygotes. This line was backcrossed to 129S4/SvEvTac for 7 generations by the donating laboratory.
|Allele Name||targeted mutation 2, Val C Sheffield|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Arl6, ADP-ribosylation factor-like 6|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||Exons 6 and 7 were replaced with a neomycin selection cassette. RT-PCR and Western blot analysis confirmed that gene expression of both isoforms waqs disrupted.|
While maintaining a live colony, these mice are bred as heterozygotes. Males homozygous for mutation are infertile.
When using the 129(B6)-Arl6tm2Vcs/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021216 in your Materials and Methods section.