C.129-Slc25a13^tm1Lct/Mmjax

Stock number: 036928
Product name: Ctrn^-
Research areas: Metabolism Research

Description

Ctrn^-/- knockout mice have exon 10 replaced by a neomycin cassette in the Slc25a13 (solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 13 or Ctrn) gene. This strain may be useful in studies of human citrin deficiency.

Detailed description

Slc25a13 (solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator or citrin/Ctrn) encodes a member of the mitochondrial carrier family that catalyzes the exchange of mitochondrial aspartate for cytoplasmic glutamate and a proton across the inner mitochondrial membrane. Mutations in SLC25A13 are associated with age-specific clinical presentations including neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type II citrullinemia (CTLN2), a disease characterized by a liver-specific decrease of argininocuccinate synthetase (ASS) resulting in citrullinemia and hyperammonemia as well neuropsychiatric symptoms.

Ctrn^-/- KO mice have exon 10 replaced by a neomycin cassette resulting in a null allele. Mice heterozygous for the mutation are viable and fertile. On the BALB background, mice infected with HK213 (an H5N1 virus) do not develop increased CCL2 pro-inflammatory cytokine levels and morbidity or mortality are not affected as compared to controls. BALB Ctrn-/- mice have not been tested for metabolic deficits. On the C57BL/6 background (B6.129-Slc25a13^tm1Lct/TsahMmjax, MMRRC Stock No. 069593), homozygous null mice exhibit hypoglycemia, decreased insulin levels and increased liver triglycerides, as well as defects in ureogenesis and gluconeogenesis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described.

Development

The targeting vector was designed to replace a 347 bp region containing exon 10 with a PGK-neomycin cassette (in the opposite orientation) in the Slc25a13 gene on chromosome 6. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred with 129S1/SvImJ females. Mice were then backcrossed to BALB/cAnNCrl mice for 12 generations and then intercrossed to obtain homozygous males for sperm cryopreservation. Recovered mice were bred to BALB/cByJ inbred mice (Stock No. 001026) for at least one generation to establish the colony.

Allele

Symbol: Slc25a13^tm1Lct
Name: targeted mutation 1, Lap-Chee Tsui
MGI accession ID: MGI:3028639
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Ctrn ^-/-
Marker symbol: Slc25a13
Marker name: solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 13
Marker synonyms: ARALAR2; citrin; CTLN2; Ctrn; NICCD; RGD1565889
Chromosome: 6
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A 347 bp region containing exon 10 was replaced with a neomycin resistance gene inserted in opposite orientation. Absence of mRNA transcript was confirmed by Northern blot and absence of protein product by Western blot analysis.