B6.129S4-Ndufs4^tm1.1Rpa/J

Stock number: 027058
Research areas: Dermatology Research, Developmental Biology Research, Neurobiology Research, Sensorineural Research

Description

Exon 2 of the mouse Ndufs4 gene has been excised in this knockout allele, useful in studies of mitochondrial disorders.

Detailed description

Mitochondrial complex I (CI)-associated defects are the most common mitochondrial disorders. Defects in the non-enzymatic, nuclear-encoded CI protein NDUFS4 (NADH dehydrogenase (ubiquinone) Fe-S protein 4) cause a Leigh-like phenotype in humans that results in death within 3–16 months after birth.

Exon 2 of the mouse Ndufs4 gene has been excised in this knockout allele. Homozygous knockout mice are smaller than normal and begin losing body hair by postnatal day 21 (P21). Hair grows back during the next hair-growth cycle. Animals have normal locomotor activity during both day and night until approximately P30, after which they become lethargic. Knockout mice are blind and cataracts sometimes appear in one or both eyes as early as P20. After P35, some knockout mice are unable to open their eyes completely and, with variable time of onset, there is a rapid decline in acoustic startle response. Starting around P35, the homozygous knockout mice develop severe ataxia. Between P35 and P50, the knockout mice stop gaining weight, display worsened ataxia, cease grooming, and die. Homozygous knockout mice die by P55 and are infertile; heterozygotes appear normal for at least a year.

Development

Exon 2, encoding the last part of a mitochondrial targeting sequence and the first 17 amino acids of the mature protein, was flanked by loxP sites and an FRT-flanked SV-Neo cassette was introduced to intron 5 using 129S4/SvJaeSor-derived AK18.1 embryonic stem (ES) cells. Resultant mice were crossed with Gt(ROSA)26Sor-FLPo mice (see Stock No. 007844) to excise the neo cassette. Exon 2 was deleted via crosses with germline-specific Meox2-cre; see Stock No. 003755). The line was backcrossed to C57BL/6J for more than 20 generations by the donating lab.

Allele

Symbol: Ndufs4^tm1.1Rpa
Name: targeted mutation 1.1, Richard D Palmiter
MGI accession ID: MGI:3793713
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Ndufs4 KO; Ndufs4^delta
Marker symbol: Ndufs4
Marker name: NADH:ubiquinone oxidoreductase core subunit S4
Marker synonyms: 6720411N02Rik; AQDQ; C1-18k; CI-18; CI-18 kDa; CI-AQDQ; MC1DN1
Chromosome: 13
Strain of origin: 129S4/SvJaeSor
Molecular note: Germ line, cre mediated recombination was used to remove exon 2, which contains the mitochondrial targeting sequence. The absence of protein product was confirmed by western blot analysis.