NDUFS4: creation of a mouse model mimicking a Complex I disorder.
The Complex I NADH dehydrogenase-ubiquinone-FeS 4 (NDUFS4) subunit gene is involved in proper Complex I function such that the loss of NDUFS4 decreases Complex I activity resulting in mitochondrial disease. Therefore, a mouse model harboring a point mutation in the NDUFS4 gene was created. An embryonic lethal phenotype was observed in homozygous (NDUFS4(-/-)) mutant fetuses. Mitochondrial function was impaired in heterozygous animals based on oxygen consumption, and Complex I activity in NDUFS4 mouse mitochondria. Decreased Complex I activity with unaltered Complex II activity, along with an accumulation of lactate, were consistent with Complex I disorders in this mouse model.
Ingraham
Christopher A
CA
Department of Biomedical Genetics, Univ. of Rochester Medical Center, Rochester, NY, USA.
Burwell
Lindsay S
LS
Skalska
Jolanta
J
Brookes
Paul S
PS
Howell
Robert L
RL
Sheu
Shey-Shing
SS
Pinkert
Carl A
CA
D000818:Animals; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology*; D017354:Point Mutation
C534449:Ndufs4 protein, mouse; D042967:Electron Transport Complex I