NDUFS4: Creation of a mouse model mimicking a Complex I disorder

被引：53

作者：

Ingraham, Christopher A. ^{[2
]}

Burwell, Lindsay S. ^{[3
]}

Skalska, Jolanta ^{[4
]}

Brookes, Paul S. ^{[5
]}

Howell, Robert L. ^{[6
]}

Sheu, Shey-Shing ^{[4
]}

Pinkert, Carl A. ^{[1
,6
]}

机构：

[1] Auburn Univ, Coll Vet Med, Dept Pathobiol, Auburn, AL 36849 USA

[2] Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA

[3] Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA

[4] Univ Rochester, Med Ctr, Dept Pharmacol & Physiol, Rochester, NY 14642 USA

[5] Univ Rochester, Med Ctr, Dept Anesthesiol, Rochester, NY 14642 USA

[6] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA

来源：

MITOCHONDRION | 2009年 / 9卷 / 03期

关键词：

Gene targeting; Knock-in; Leigh syndrome; Leigh's disease; AQDQ SUBUNIT; MITOCHONDRIAL PROLIFERATION; OXIDATIVE-PHOSPHORYLATION; MUTATIONS; DEFICIENCY; GENE; MICE; PATIENT;

D O I：

10.1016/j.mito.2009.02.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. (C) 2009 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

引用

页码：204 / 210

页数：7

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