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Ectopic expression of BBS1 rescues male infertility, but not retinal degeneration, in a BBS1 mouse model

Citation

Cring, Matthew (2020), Ectopic expression of BBS1 rescues male infertility, but not retinal degeneration, in a BBS1 mouse model , Dryad, Dataset, https://doi.org/10.5061/dryad.2rbnzs7jm

Abstract

Bardet-Biedl syndrome (BBS) is a rare ciliopathy for which there are no current effective treatments. BBS is a genetically heterogeneous disease, though the M390R mutation in BBS1 is involved in approximately 25% of all genetic diagnoses of BBS. The principle features of BBS include retinal degeneration, obesity, male infertility, polydactyly, intellectual disability, and renal abnormalities. Patients with mutations in BBS genes often present with night blindness within the first decade of life, which progresses to complete blindness. This is due to progressive loss of photoreceptor cells. Male infertility is caused by a lack of spermatozoa flagella, rendering them immobile. In this study, we have crossed the wild-type human BBS1 gene, driven by the CAG promoter, onto the Bbs1M390R/M390R mouse model to determine if ectopic expression of BBS1 rescues male infertility and retinal degeneration. qRT-PCR indicates that the BBS1 transgene is expressed in multiple tissues throughout the mouse, with the highest expression seen in the testes, and much lower expression in the eye and hypothalamus. Immunohistochemistry of the transgene in the eye showed little if any expression in the photoreceptor outer nuclear layer. When male Bbs1M30R/M390R;BBS1TG+mice are housed with WT females, they are able to sire offspring, indicating that the male infertility phenotype of BBS is rescued by the transgene. Using electroretinography (ERGs) to measure retinal function and optical coherence tomography to measure retinal thickness, we show that the transgene does not confer protection against retinal degeneration in Bbs1M300R/M390R;BBS1TG+ mice.

Usage Notes

Missing values for eyes in OCT data sheet are due to un-readable images. In the case where there is only data for one eye, that value was used for analysis. Otherwise, the average of two eyes was used in our analyses.

Funding

National Institutes of Health, Award: EY011298

National Institutes of Health, Award: EY017168

National Institutes of Health, Award: P30EY025580