Ndufs4 KO Mouse

The NDUFS4 gene encodes a nuclear-encoded accessory subunit of NADH dehydrogenase (Complex I), a vital component of the mitochondrial electron transport chain. The protein product, NDUFS4, is an 18 kDa peripheral membrane protein located on the matrix side of the inner mitochondrial membrane, crucial for the proper assembly, stability, and full catalytic activity of Complex I, though it is not directly involved in catalysis ^[1]. NDUFS4 is widely expressed, particularly in tissues with high energy demands such as the brain, heart, and skeletal muscle. Its expression is tightly regulated at both transcript and protein levels, with alternative splicing and post-translational modifications like phosphorylation influencing its mitochondrial import and complex assembly ^[1-3]. Mutations in the NDUFS4 gene are a significant cause of mitochondrial complex I deficiency, which can manifest as various severe neurological and metabolic disorders, most notably Leigh Syndrome ^[1]. Other associated conditions include Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy, lactic acidosis, and stroke (MELAS), and some forms of Parkinson's disease, all highlighting the critical role of NDUFS4 in cellular energy production and overall mitochondrial homeostasis ^[2-4].

The Ndufs4 KO mouse is a gene knockout model created using gene-editing techniques to knock out the Exon 2 of the Ndufs4 gene (the homolog of the human NDUFS4 gene) in mice. Homozygous Ndufs4 KO mice begin to exhibit phenotypes around 3 weeks of age, rendering them unable to breed offspring. This model can be used to study the pathogenic mechanisms of Leigh Syndrome, Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy, lactic acidosis, and stroke (MELAS), and some forms of Parkinson's disease, providing a research basis for developing related therapeutic interventions.