Journal article
Progressive retinal degeneration of rods and cones in a Bardet-Biedl syndrome type 10 mouse model
Disease models & mechanisms, Vol.15(9), dmm049473
09/01/2022
DOI: 10.1242/dmm.049473
PMCID: PMC9536196
PMID: 36125046
Appears in UI Libraries Support Open Access
Abstract
Bardet-Biedl syndrome (BBS) is a multi-organ autosomal-recessive disorder caused by mutations in at least 22 different genes. A constant feature is early-onset retinal degeneration leading to blindness. Among the most common forms is BBS type 10 (BBS10), which is caused by mutations in a gene encoding a chaperonin-like protein. To aid in developing treatments, we phenotyped a Bbs10 knockout (Bbs10−/−) mouse model. Analysis by optical coherence tomography (OCT), electroretinography (ERG) and a visually guided swim assay (VGSA) revealed a progressive degeneration (from P19 to 8 months of age) of the outer nuclear layer that is visible by OCT and histology. Cone ERG was absent from at least P30, at which time rod ERG was reduced to 74.4% of control levels; at 8 months, rod ERG was 2.3% of that of controls. VGSA demonstrated loss of functional vision at 9 months. These phenotypes progressed more rapidly than retinal degeneration in the Bbs1M390R/M390R knock-in mouse. This study defines endpoints for preclinical trials that can be utilized to detect a treatment effect in the Bbs10−/− mouse and extrapolated to human clinical trials.
Details
- Title: Subtitle
- Progressive retinal degeneration of rods and cones in a Bardet-Biedl syndrome type 10 mouse model
- Creators
- Sara K MayerJacintha ThomasMegan HelmsAishwarya KothapalliIoana CherascuAdisa SalesevicElliot StalterKai WangPoppy DattaCharles SearbySeongjin SeoYing HsuSajag BhattaraiVal C SheffieldArlene V Drack
- Resource Type
- Journal article
- Publication Details
- Disease models & mechanisms, Vol.15(9), dmm049473
- DOI
- 10.1242/dmm.049473
- PMID
- 36125046
- PMCID
- PMC9536196
- NLM abbreviation
- Dis Model Mech
- ISSN
- 1754-8403
- eISSN
- 1754-8411
- Publisher
- The Company of Biologists
- Grant note
- name: Fighting Blindness Canada; name: Bardet Biedl Syndrome Family Association; name: Ronald Keech Professorship; name: InVision 20/20; DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 EY022616, P30 EY025580; DOI: 10.13039/100008893, name: University of Iowa
- Language
- English
- Date published
- 09/01/2022
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984297158302771
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