Journal article
A novel porcine model of CLN3 Batten disease recapitulates clinical phenotypes
Disease models & mechanisms, Vol.16(8), dmm050038
08/2023
DOI: 10.1242/dmm.050038
PMCID: PMC10434985
PMID: 37305926
Abstract
Mouse models of CLN3 Batten disease, a rare lysosomal storage disorder with no cure, have improved our understanding of CLN3 biology and therapeutics through their ease of use and a consistent display of cellular pathology. However, the translatability of murine models is limited by disparities in anatomy, body size, life span, and inconsistent, subtle behavior deficits that can be difficult to detect in CLN3 mutant mouse models, limiting their utility in preclinical studies. Here we present a longitudinal characterization of a novel miniswine model of CLN3 disease that recapitulates the most common human pathogenic variant, an exon 7-8 deletion (CLN3Δex7/8). Progressive pathology and neuron loss is observed in various regions of the CLN3Δex7/8 miniswine brain and retina. Additionally, mutant miniswine present with retinal degeneration and motor abnormalities, similar to deficits seen in human patients. Taken together, the CLN3Δex7/8 miniswine model shows consistent and progressive Batten disease pathology and behavioral impairment mirroring clinical presentation, demonstrating its value in studying the role of CLN3 and safety/efficacy of novel disease modifying therapeutics.
Details
- Title: Subtitle
- A novel porcine model of CLN3 Batten disease recapitulates clinical phenotypes
- Creators
- Vicki J Swier - Sanford ResearchKatherine A White - Sanford ResearchTyler B Johnson - Sanford ResearchXiaojun Wang - Exemplar Genetics (United States)Jimin Han - University of Rochester Medical CenterDavid A Pearce - Sanford ResearchRuchira Singh - University of Rochester Medical CenterArlene V Drack - University of IowaWanda Pfeifer - University of IowaChristopher S Rogers - Exemplar Genetics (United States)Jon J Brudvig - Sanford ResearchJill M Weimer - University of South Dakota
- Resource Type
- Journal article
- Publication Details
- Disease models & mechanisms, Vol.16(8), dmm050038
- DOI
- 10.1242/dmm.050038
- PMID
- 37305926
- PMCID
- PMC10434985
- NLM abbreviation
- Dis Model Mech
- eISSN
- 1754-8411
- Grant note
- DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: NS081877; DOI: 10.13039/100000053, name: National Eye Institute, award: R01EY028167, R01EY030183, R01EY033192, R21EY027750; name: Forebatten Foundation; DOI: 10.13039/100001818, name: Research to Prevent Blindness; DOI: 10.13039/100008893, name: University of Iowa; DOI: 10.13039/100011411, name: University of South Dakota; DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: P20GM103548, P20GM121341
- Language
- English
- Electronic publication date
- 06/12/2023
- Date published
- 08/2023
- Academic Unit
- Stead Family Department of Pediatrics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984433848502771