10.5061/DRYAD.2RBNZS7JM
Cring, Matthew
0000-0001-9017-7683
University of Iowa
Ectopic expression of BBS1 rescues male infertility, but not retinal
degeneration, in a BBS1 mouse model
Dryad
dataset
2020
Mouse models
Sperm
Eyes
Retinal degeneration
Bardet-Biedl syndrome (BBS)
Genetically modified animals
National Eye Institute
https://ror.org/03wkg3b53
EY011298
National Eye Institute
https://ror.org/03wkg3b53
EY017168
National Eye Institute
https://ror.org/03wkg3b53
P30EY025580
2020-03-04T00:00:00Z
2020-03-04T00:00:00Z
en
58847 bytes
6
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
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.
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.