B6;129S-Maoa^K284stop Maob^tm1Shih/J

Stock number: 014134
Research areas: Developmental Biology Research, Neurobiology Research

Description

This strain harbors mutations in the Maob and Maob genes which abolish gene function. These mice exhibit increased reactivity to stress,increased aggression and may be useful for studying MAOA and MAOB-related behaviors and disorders.

Detailed description

This strain carries two mutant alleles, a knockout of the X-linked monoamine oxidase B (Maob) gene and a spontaneous mutation designated Maoa^K284stop in the monoamine oxidase A (Maoa) gene. The two mutations lie 24kb apart. MAO A/B deficient mice are viable, fertile, and normal in size. Maoa and Maob are mitochondrial enzymes which oxidize neurotransmitters and dietary amines. These mutants lack both MAOA and MAOB activity in the brain and liver resulting in increased levels of phenylethylamine, serotonin, dopamine, and norepinephrine. These mice exhibit increased reactivity to stress and increased aggression. These mice may be useful for studying MAOA and MAOB-related behaviors and disorders.

Development

A targeting vector was designed to replace exon 6 of the X-linked monoamine oxidase B (Maob) gene with a neomycin resistance (neo) cassette. The construct was electroporated into either 129S/SvEv-derived CCE embryonic stem (ES) cells or 129S4/SvJae-derived CCE ES cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to 129/Sv females. The male offspring were backcrossed at least 25 generations to 129/Sv females resulting in Maob deficient mice (Stock No. 014133). A mutation, designated Maoa^K284stop, arose spontaneously in exon 8 of the X-linked monoamine oxidase A (Maoa) gene of one male animal. This mutation was caused by a transversion at nucleotide 863, resulting in a premature stop codon at residue 284. This mutant male was backcrossed to a 129/Sv female, and the resulting female offspring were bred to 129/Sv males. Half of the resulting male offspring carried both mutations. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 4 of the 27 markers throughout the genome suggested a C57BL/6 genetic contribution from an unknown source.

Allele

Symbol: Maoa^K284stop
Name: K284stop
MGI accession ID: MGI:3057337
Generation method: Spontaneous
Marker symbol: Maoa
Marker name: monoamine oxidase A
Chromosome: X
Strain of origin: 129S6/SvEvTac
Molecular note: An A-to-T at coding nucleotide 850 in exon 8 created a stop codon at lysine codon 284 (p.K284*).

Allele

Symbol: Maob^tm1Shih
Name: targeted mutation 1, Jean C Shih
MGI accession ID: MGI:2180752
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Maob
Marker name: monoamine oxidase B
Chromosome: X
Strain of origin: 129S/Sv
Molecular note: The gene was disrupted by insertion of a neo cassette into exon 6 via homologous recombination resulting in a premature stop codon and protein truncation. Enzyme assays of brain and liver extracts from mutant mice demonstrated background levels of enzyme activity. Western blot and immunohistochemical analyses failed to detect protein product.
General note: ES cell line = CCE (129S/SvEv-Gpi1^c) or J1 (129S4/SvJae).