Journal article
Ectopic expression of BBS1 rescues male infertility, but not retinal degeneration, in a BBS1 mouse model
Gene therapy, Vol.29(5), pp.227-235
03/04/2021
DOI: 10.1038/s41434-021-00241-1
PMID: 33664503
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 ~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 Bbs1
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 Bbs1
;BBS1
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 Bbs1
;BBS1
mice. The results of this study indicate that the male infertility aspect of BBS is an attractive target for gene therapy.
Details
- Title: Subtitle
- Ectopic expression of BBS1 rescues male infertility, but not retinal degeneration, in a BBS1 mouse model
- Creators
- Matthew R Cring - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USAKacie J Meyer - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA, USACharles C Searby - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USAAdam Hedberg-Buenz - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA, USAMichael Cave - Division of Medical Genetics and Genomics, Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USAMichael G Anderson - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA, USAKai Wang - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USAVal C Sheffield - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. val-sheffield@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Gene therapy, Vol.29(5), pp.227-235
- DOI
- 10.1038/s41434-021-00241-1
- PMID
- 33664503
- NLM abbreviation
- Gene Ther
- ISSN
- 0969-7128
- eISSN
- 1476-5462
- Publisher
- England
- Language
- English
- Electronic publication date
- 03/04/2021
- Academic Unit
- Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984071958602771
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