Strain Name:
Stock Number:
Citation ID:
Other Names:
Ndufa1S55A-129Svj, Ndufa1S55A-Balb/c, Ndufa1 knock-in model for Complex I deficiency

Gene Information

Allele: Ndufa1tm1Nay (Mus musculus (mouse))
Name: NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, targeted mutation 1, Nagendra Yadava
Chromosome: X
Alteration at locus: Knock-In
Monarch Initiative (Disease and Phenotype Associations):
Gene: Ndufa1 (Mus musculus (mouse))
Name: NADH:ubiquinone oxidoreductase subunit A1
Synonyms: MWFE, 1810049F12Rik
Chromosome: X
Alteration at locus: Knock-In
Monarch Initiative (Disease and Phenotype Associations): MGI:1929511
Genetic Alterations
Missense mutation in the Ndufa1 gene (MGI:1929511) in codon 55 (T>G; codon TCT>GCT), replacing serine-55 with alanine (p.S55A) in the MWFE subunit of Complex I.

Alteration details: 
  • mRNA RefSeq: NM_019443.2
  • nucleic acid level: c.163T>G
  • protein level: p.Ser55Ala
Genotype Determination
ES Cell Line
iTL1 derived from 129S6/SvEvTac

Homozygous: Mutant females show improved survival despite the presence of systemic partial respiratory chain Complex I deficiency (published). Abnormal mammary gland ductal architecture (unpublished)

Hetero/Hemizygous: Mutant males display glucose intolerance (unpublished) and reduced respiratory exchange ratio (RER) and produced less body heat. They are hypo-active and eat less. Despite eating less their weight gain is comparable or relatively more. The showed age-dependent Purkinje neurons' degeneration.

MeSH Terms
    Strain Development
    129/SvEv-derived male embryonic stem cells (ES) were used to target the Ndufa1S55A allele on its native locus at X-chromosome. The Ndufa1S55A allele harbors a point mutation in the codon-55 (T>G; codon TCT>GCT). The long homology arm was 6.0 kb upstream to the point mutation (T>G) in exon 2. The LoxP/FRT-Neo cassette for G418 selection was inserted 903 bp downstream of the point mutation within intron 2-3. The short homology arm extended 2.0 kb from the 5’-end of the Neo cassette. The T>G mutation was created by site-directed mutagenesis. ES clones with correct targeting by homologous recombination were screened first by polymerase chain reaction (PCR) and later confirmed by Southern blot analysis with an internal probe. Genomic DNA was digested with HpaI, and electrophoretically separated on a 0.8% agarose gel. After transfer to a nylon membrane, the digested DNA was hybridized with a probe targeted against the 3’ internal region. DNA from 129/SvEv was used as wild-type control. The expected sizes for wild-type (WT; 9.3 kb) and knock-in (KI Neo: 11 kb) were observed. Because ES cells were derived from male mice, only one copy of the Ndufa1 gene was expected. Therefore, correct targeting will result in only one band of 11 kb. By Southern blot analysis clone #253 was identified to have Ndufa1S55A allele correctly targeted at its native locus. After confirming the reduced MWFE and Complex I levels in ES clone #253, it was injected into C57BL/6 blastocysts. 

    Chimeras with high percentage agouti coat color were mated to 129 FLP mice (JAX #003946) to remove the Neo-cassette and simultaneously generate the germ-line founder mice. A mutant male (Ndufa1S55A/Y) and two heterozygous females (Ndufa1S55A/+) were obtained. They were crossed with wild-type mice (129S1/SvImJ, JAX #02448) to expand the colony. The deletion of Neo-cassette was confirmed by PCR screening using primers set F1 (5’-CAA AGC CAT TTC TCT GCC TCT-3’) and R1 (5’-CCA AAA AAC CTC ACT CAC AAC C-3’). The presence of Ndufa1S55A allele was confirmed using primers set F2 (5’ -TGA GCT ATC TCT TCA GCC TCT AG- 3’) and R2 (5’-GAC CCT GTC TCA ATT ACA AAT CAA CCA ACC -3’) by Hyp188III restriction fragment length polymorphism. The enzyme cuts only the wild-type (Ndufa1+) allele. Finally, the presence of T>G mutation in the Ndufa1S55A mice was confirmed by DNA sequencing. From gene targeting to founder mice generation, this project was supported by inGenious Targeting Laboratory (Stony Brook, NY) on a pay-for-service basis.

    To transfer the Ndufa1S55A allele on BALB/c genetic background, we performed 9 generations of backcrossing. Because the Ndufa1 gene is X-chromosome linked, we crossed Ndufa1S55A-129S1 mutant males (r/Y) mice (from N5) with wild-type BALB/c females (X/X). Such a cross resulted in heterozygous females (r/X), which were mated with wild-type BALB/c males (X/Y). Then in the next generation, mutant male progeny (r/Y) were mated with wild-type BALB/c females (X/X). This alternating breeding scheme continued for another 8 generations (i.e., N9) to generate Ndufa1S55A-BALB/c strain.
    Suggested Control Mice
    Wild-type littermates
    • Apoptosis
    • Cancer
    • Cardiovascular
    • Cell Biology
    • Developmental Biology
    • Diabetes
    • Endocrine Deficiency
    • Hematology
    • Immunology and Inflammation
    • Internal_Organ
    • Metabolism
    • Models for Human Disease
    • Neurobiology
    • Obesity
    • Research Tools
    • Sensorineural
    Nagendra Yadava, Ph.D., Baystate Medical Center.

    Colony and Husbandry Information

    Mice derived from requested cell lines via Microinjection services will be pathogen tested prior to delivery of mice and health reports will be provided. If you require additional health status information prior to requesting microinjection please email
    Coat Color
    agouti (A/A)
    MMRRC Breeding System
    Breeding Scheme(s)
    All possible breeding strategy can be used. Wild-type and mutant colony can be bred separately. In this case, no genotyping of progeny will be required. Alternatively, heterozygous females with wild-type males can be bred. However, in this case genotyping will be required.
    Overall Breeding Performance
    NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Yes X-linked
    Homozygotes are fertile: Yes Yes
    Hetero/Hemizygotes are fertile: Yes Yes
    Age Reproductive Decline: 4 to 6 months 4 to 6 months
    Bred to Homozygosity
    Average litter size
    Recommended wean age
    3 weeks
    Average Pups Weaned

    Order Request Information

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