B6;129S-Maob^tm1Shih/J

Stock number: 014133
Research areas: Developmental Biology Research, Neurobiology Research

Description

In this knockout strain, a neomycin resistance cassette replaces exon 6 of the Maob gene, abolishing gene function. These mice may be useful for studying neurodegeneration and MAOB-related behaviors.

Detailed description

In this strain, a neomycin resistance (neo) cassette replaces exon 6 of the endogenous X-linked monoamine oxidase B (Maob) gene, abolishing gene function. Maob deficient mice are viable, fertile, and normal in size. Maob is a mitochondrial enzyme which oxidizes neurotransmitters and dietary amines. These mutants lack MAOB activity in the brain and liver resulting in increased levels of phenylethylamine. These mice exhibit increased reactivity to stress and increased aggression. These mice also show decreased susceptibility to the neurodegenerative effects of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), which induces Parkinson's disease-like symptoms when administered to mice. These mice may be useful for studying neurodegeneration and MAOB-related behaviors.

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. 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. Three of the 27 markers throughout the genome suggested a C57BL/6 genetic contribution from an unknown source.

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).