129-Comt^{tm2(COMT)Xzho}/J

Stock number: 027993
Product name: Met/Met
Strain synonyms: Human COMT Met, COMTVal158Met
Research areas: Neurobiology Research

Description

Human COMT Met mice have human COMT gene replacing the entire coding region of the endogenous gene. They also contain a methionine mutation, Val158Met, commonly associated with schizophrenia and other psychiatric disorders.

Detailed description

Human COMT Met mice contain human catechol-O-methyltransferase (Comt) gene replacing the endogenous coding region. They also contain a missense mutation in exon 3, corresponding with human codon 158, resulting in the Val158Met mutation commonly associated with schizophrenia and other psychiatric disorders. Membrane bound COMT is highly expressed in both prefrontal cortex and hippocampus and is a key enzyme in catecholamine clearance from the synapse. COMT helps maintain appropriate levels of neurotransmitters, such as such as dopamine and norepinephrine, in prefrontal cortex. Mutations and increased frequency of this gene are associated with schizophrenia, anxiety, mood disorders, obsessive-compulsive disorder, and attention deficit disorder. Homozygous Human COMT Met mice are viable and fertile. The donating investigator reports a lack of phenotype on this 129 genetic background (July 2018). We may modify the strain description if necessary as any results become available.

Of note, this allele is also available on a C57BL/6J congenic background as Stock No. 032383. The congenic B6J strain show behavioral phenotypes consistent with those seen in patients with schizophrenia and other psychiatric disorders.

Companion strains, containing containing a WT human COMT gene, are available on a congenic B6J background (Stock No. 032382) and a 129 coisogenic background (Stock No. 027990).

Development

The Human COMT Met targeting construct was designed to replace the entire endogenous catechol-O-methyltransferase (Comt) coding region with human Comt sequence following by a neomycin (neo) resistance cassette. A missense mutation was introduced in exon 3, corresponding with human codon 158, resulting in the Val158Met mutation commonly associated with schizophrenia and other psychiatric disorders. This targeting construct was electroporated into 129Sv-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. Human COMT Met mice were maintained on a 129Sv background. Upon arrival at The Jackson Laboratory, mutant mice were bred to 129S1/SvImJ (Stock No. 002448) mice for at least one generation to establish the colony.

Allele

Symbol: Comt^{tm2(COMT)Xzho}
Name: targeted mutation 1, Xianjin Zhou
MGI accession ID: MGI:5661843
Generation method: Targeted
Attributes: Null/Knockout; Inserted expressed sequence
Synonyms: Human COMT Met
Marker symbol: Comt
Marker name: catechol-O-methyltransferase
Marker synonyms: Comt1; D16Wsu103e; D330014B15Rik; HEL-S-98n
Chromosome: 16
Strain of origin: 129
Expressed genes: COMT,catechol-O-methyltransferase,human
Site of expression: Human COMT is expressed in both prefrontal cortex and hippocampus.
Molecular note: The targeting construct was designed to replace the entire endogenous coding region with the human sequence following by a neomycin (neo) resistance cassette. A missense mutation was introduced in exon 3, corresponding with human codon 158, resulting in the Val158Met mutation commonly associated with schizophrenia and other psychiatric disorders. Western blot analysis confirmed the absence of protein expression in the hippocampus and cortex.