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Sdha+/- Rats Display Minimal Muscle Pathology Without Significant Behavioral or Biochemical Abnormalities. J Neuropathol Exp Neurol 2018 Aug 01;77(8):665-672 PMID: 29850869 PMCID: PMC6044411

Pubmed ID



Mitochondrial diseases (MDs) result from alteration of the mitochondrial respiratory chain (MRC) function. Despite the prevalence of MDs in the population, the paucity of animal models available limits the understanding of these disorders. Mutations in SDHA, a gene that codes for the alpha subunit of succinate dehydrogenase (SDH), can cause some forms of MD. SDHA is a crucial contributor to MRC function. In order to expand the range of MD animal models available, we attempted to generate a Sdha knockout rat. Since homozygous Sdha-/- rats could neither be identified in newborn litters, nor as early as embryonic day 14, we evaluated wild-type (WT) and heterozygous Sdha+/- genotypes. No differences in behavioral, biochemical, or molecular evaluations were observed between WT and Sdha+/- rats at 6 weeks or 6 months of age. However, 30% of Sdha+/- rats displayed mild muscle fiber atrophy with rare fibers negative for cytochrome oxidase and SDH on histochemical staining. Collectively, our data provide additional evidence that modeling SDH mutations in rodents may be challenging due to animal viability, and heterozygous rats are insufficiently symptomatic at a phenotypic and molecular level to be of significant use in the study of SDH deficiency.

Author List

Siebers EM, Choi MJ, Tinklenberg JA, Beatka MJ, Ayres S, Meng H, Helbling DC, Takizawa A, Bennett B, Garces AM, Dias Duarte Machado LG, Dimmock D, Dwinell MR, Geurts AM, Lawlor MW


Brian Bennett D.Phil. Professor and Chair in the Physics department at Marquette University
Melinda R. Dwinell PhD Center Associate Director, Associate Professor in the Physiology department at Medical College of Wisconsin
Aron Geurts PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Michael W. Lawlor MD, PhD Associate Professor in the Pathology department at Medical College of Wisconsin

jenkins-FCD Prod-296 4db9d02597e0a2e889e230f853b641c12f1c3ee3