Journal article
Effect of genetic background on phenotype variability in transgenic mouse models of amyotrophic lateral sclerosis: A window of opportunity in the search for genetic modifiers
Amyotrophic lateral sclerosis, v 12(2)
01 Mar 2011
PMID: 21241159
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Transgenic (Tg) mouse models of FALS containing mutant human SOD1 genes (G37R, G85R, D90A, or G93A missense mutations or truncated SOD1) exhibit progressive neurodegeneration of the motor system that bears a striking resemblance to ALS, both clinically and pathologically. The most utilized and best characterized Tg mice are the G93A mutant hSOD1 (Tg(hSOD1-G93A)1GUR mice), abbreviated G93A. In this review we highlight what is known about background-dependent differences in disease phenotype in transgenic mice that carry mutated human or mouse SOD1. Expression of G93A-hSOD1Tg in congenic lines with ALR, NOD.Rag1KO, SJL or C3H backgrounds show a more severe phenotype than in the mixed (B6xSJL) hSOD1Tg mice, whereas a milder phenotype is observed in B6, B10, BALB/c and DBA inbred lines. We hypothesize that the background differences are due to disease-modifying genes. Identification of modifier genes can highlight intracellular pathways already suspected to be involved in motor neuron degeneration; it may also point to new pathways and processes that have not yet been considered. Most importantly, identified modifier genes provide new targets for the development of therapies.
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Details
- Title
- Effect of genetic background on phenotype variability in transgenic mouse models of amyotrophic lateral sclerosis: A window of opportunity in the search for genetic modifiers
- Creators
- Terry D. Heiman-Patterson - Drexel UniversityRoger B. Sher - Jackson LaboratoryElizabeth A. Blankenhorn - Drexel UniversityGuillermo Alexander - Drexel UniversityJeffrey S. Deitch - Drexel UniversityCatherine B. Kunst - Roosevelt InstituteNicholas Maragakis - Johns Hopkins UniversityGregory Cox - Jackson Laboratory
- Publication Details
- Amyotrophic lateral sclerosis, v 12(2)
- Publisher
- Taylor & Francis
- Number of pages
- 8
- Grant note
- ALS Hope Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; [Retired Faculty]
- Web of Science ID
- WOS:000287402100001
- Scopus ID
- 2-s2.0-79951754463
- Other Identifier
- 991019169709804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology