C57BL/6-Crb1⁺ Kmo^{tm1a(KOMP)Wtsi}/NagarMmjax

Stock number: 034016
Product name: KMO KO

Research areas: Metabolism Research, Neurobiology Research, Research Tools

Description

KMO KO mice carry the knock-out first/lacZ reporter allele of the Kmo [kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)] gene and exhibit increased levels of kynurenine pathway metabolites and low levels of neurotoxic 3-hydroxykynurenine (3OHKYN). This strain may be useful in studies of the kynurenine pathway, reactive oxygen species (ROS), and glaucoma.

Detailed description

Kmo [kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)] encodes a mitochondrion outer membrane enzyme that catalyzes the hydroxylation of the L-tryptophan metabolite, L-kynurenine, to form neurotoxic 3-hydroxykynurenine (3OHKYN). 3OHKYN is a reactive oxygen species (ROS) generator and is associated with several neurological diseases including Huntingtin's disease. Kmo is predominantly expressed in brain, liver and kidney. Kmo knock-in/knock-out mice contain a lacZ/neomycin cassette and a loxP-flanked exon 5. The spontaneous mutation Crb1^rd8 (retinal degeneration 8), a strain characteristic of the C57BL/6N strain has been bred out of the colony. Homozygous mice are viable and fertile and exhibit increased levels of kynurenine pathway metabolites kynurenine, anthranilic acid and kynurenic acid in the brain and retina, and mildly elevated fasted blood glucose. Retinal ischemia/reperfusion (I/R) injury results in reduced loss of retinal ganglion cells in KMO KO mice. This strain may be useful in studies of the kynurenine pathway, ROS, and glaucoma.

Development

Embryonic stem (ES) cells carrying the Kmo^{tm1a(KOMP)Wtsi} knock-out first allele with a promoter-driven selection cassette were acquired from KOMP. This allele, incorporating an FRT-lacZ-loxP-neomycin-FRT-loxP cassette in intron 4 and a loxP site in intron 5 of the mouse Kmo gene, was created in JM8A1.N4 C57BL/6N-derived ES cells. Resultant chimeric mice were crossed with C57BL/6J mice to detect germline transmission and screened for the presence of the Crb1^rd8 allele, a spontaneous mutation found in the C57BL/6N strain. The donating laboratory subsequently bred the line to C57BL/6J mice for an unknown number of generations and eliminated the rd8 allele from the colony. Upon arrival, mice were bred to C57BL/6J for at least one generation to establish the colony.

Allele

Symbol: Crb1⁺
Name: wild type
MGI accession ID: MGI:2441358
Generation method: Not Applicable
Marker symbol: Crb1
Marker name: crumbs family member 1, photoreceptor morphogenesis associated
Marker synonyms: 7530426H14Rik; A930008G09Rik; CRB1-A; CRB1-B; CRB1-C; LCA8; RP12
Chromosome: 1
Strain of origin: Not Applicable

Allele

Symbol: Kmo^{tm1a(KOMP)Wtsi}
Name: targeted mutation 1a, Wellcome Trust Sanger Institute
MGI accession ID: MGI:4364232
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Reporter; Null/Knockout
Synonyms: Kmo^null
Marker symbol: Kmo
Marker name: kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)
Marker synonyms: dJ317G22.1; kynurenine 3-hydroxylase
Chromosome: 1
Strain of origin: C57BL/6N
Molecular note: The L1L2_Bact_P cassette was inserted at position 175470673 of Chromosome 1 upstream of the critical exon(s) (Build GRCm39). The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by a neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site is inserted downstream of the targeted exon(s) at position 175471397. The critical exon(s) is/are thus flanked by loxP sites. A "conditional ready" (floxed) allele can be created by flp recombinase expression in mice carrying this allele. Subsequent cre expression results in a knockout mouse. If cre expression occurs without flp expression, a reporter knockout mouse will be created. Further information on targeting strategies used for this and other IKMC alleles can be found at http://www.informatics.jax.org/mgihome/nomen/IKMC_schematics.shtml