C57BL/6J-Nadk2^nmf421/JRwbJ

Stock number: 037020
Product name: Nadk2^-/-; nmf421 S330P

Strain synonyms: nmf421
Research areas: Developmental Biology Research, Neurobiology Research

Description

Nadk2^nmf421 mice carry a recessive ENU-induced mutation that results in a 65% reduction of NADK2 protein. Mice homozygous for the mutation (Nadk2^-/-) exhibit neuromuscular degeneration, neurodegeneration, and metabolic defects. Homozygotes begin dying by 3-4 months of age.

Detailed description

Nadk2 (NAD kinase 2, mitochondrial) encodes the mitochondrial form of nicotinamide adenine dinucleotide (NAD) kinase. NADK2 catalyzes the phosphorylation of NAD to generate NADP. Nmf421 is a recessive ENU-induced mutation in Nadk2 with a serine to proline point mutation (S330P) in exon 11 that results in a 65.6 +/- 10% reduction of NADK2 protein expression. Mice homozygous for nmf421 (designated Nadk2-/-) begin dying by 3-4 months of age.  Homozygotes are characterized by kyphosis, tremor, abnormal gait, and hind limb wasting. Denervation of neuromuscular junctions in the hind limb occurs by 5 weeks of age, muscle atrophy by 11 weeks of age. Cerebellar Purkinje cells exhibit a progressive reduction in cell density by 5 weeks of age. Metabolomics analysis indicates an elevation in plasma lysine levels and a deficiency of dienoyl-COA reductase (DECR).

Development

The nmf421 phenotypic deviant was identified following multidose ethylnitrosourea (ENU) treatments to induce mutations in male founder C57BL/6J mice (Stock No. 000664), in the Neuroscience Mutagenesis Facility (NMF) at The Jackson Laboratory. Mice were identified by hindlimb wasting, gait abnormalities, and shakiness. Sequence analysis indicates that this recessive mutation is a nucleotide substitution resulting in the replacement of serine at codon 330 with proline (S330P, c.T988C; transcript Nadk2-205) in exon 11 of the NAD kinase 2, mitochondrial (Nadk2) gene on chromosome 15. The mutation is near the C-terminal end of the catalytic domain. The colony was maintained in the laboratory of Dr. Robert Burgess at The Jackson Laboratory, it was transferred to The Jackson Laboratory Repository in 2023.

Allele

Symbol: Nadk2^nmf421
Name: neuroscience mutagenesis facility, 421
MGI accession ID: MGI:6825801
Generation method: Chemically induced (ENU)
Attributes: Hypomorph
Marker symbol: Nadk2
Marker name: NAD kinase 2, mitochondrial
Marker synonyms: 1110020G09Rik; 4933430B08Rik; C5orf33; DECRD; MNADK; NADKD1; RGD1306809
Chromosome: 15
Strain of origin: C57BL/6J
Molecular note: The phenotypic deviant was identified by by hindlimb wasting, gait abnormalities, and shakiness following multidose ethylnitrosourea (ENU) treatments. Sequence analysis indicates that this recessive mutation is a nucleotide substitution resulting in the replacement of serine at codon 330 with proline (S330P, c.T988C; transcript Nadk2-205) in exon 11. The mutation is near the C-terminal end of the catalytic domain and results in a 65.6 +/- 10% reduction of NADK2 protein expression.