Inbred FVB/N Mice Are Mutant at thecp49/Bfsp2Locus and Lack Beaded Filament Proteins in the Lens

Vladimir N. Simirskii, Robert S. Lee, Eric F. Wawrousek, Melinda K. Duncan
2006 Investigative Ophthalmology and Visual Science  
PURPOSE. FVB/N is considered an ideal inbred mouse strain for transgenic mouse production because of the ease of pronuclear microinjection and its overall fecundity. It is well established that vertebrate lens fiber cells normally express a modified intermediate filament network consisting of the proteins filensin and CP49, and it was recently reported that the mouse strain 129 harbors mutations in CP49 that have the potential to confound the interpretation of gene knockout studies of the lens.
more » ... tudies of the lens. The purpose of this study was to evaluate the status of the CP49/Bfsp2 gene in the FVB/N strain. METHODS. PCR analysis of genomic DNA was used to evaluate the status of the CP49 gene in FVB/N mice procured from the four major US distributors of these animals-Harlan Laboratories, Taconic Farms, Jackson Laboratory, and the NIH/NCI/DCT production facility run by Charles River Laboratories. The structure of the CP49 transcript was evaluated by RT-PCR, and the presence of CP49 protein in the lens was evaluated by immunofluorescence. RESULTS. FVB/N mice obtained from all four US distributors were shown to harbor a 6-kb deletion of the CP49 gene identical with that previously reported in mouse strain 129; C57BL/6 mice did not have this modification. Immunofluorescence demonstrated that FVB/N mice do not have detectable CP49 or filensin protein in the lens, whereas C57BL/6 mice have the expected protein distribution. CONCLUSIONS. In humans, mutations in the CP49/BFSP2 gene have been linked to familial, congenital cataract, demonstrating an important role of this gene in lens transparency. The demonstration that FVB/N mice lack CP49 protein in the lens suggests that it may be necessary to reevaluate the mechanisms underlying lens phenotypes obtained as a result of transgenic manipulation of this strain. (Invest Ophthalmol Vis Sci. 2006; 47:4931-4934)
doi:10.1167/iovs.06-0423 pmid:17065509 fatcat:ip62yeb4hnftzdjad4jfbsdrma