129-Comt^{tm1(COMT)Xzho}/J

Stock number: 027990
Product name: Val/Val
Strain synonyms: Human COMT Val
Research areas: Neurobiology Research

Description

Human COMT Val mice have the human COMT gene replacing the entire coding region of the endogenous gene. They may be useful when studying schizophrenia and other psychiatric disorders.

Detailed description

Human COMT Val mice contain human catechol-O-methyltransferase (Comt) gene replacing the endogenous coding region. 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 Val 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. 032382.

Companion strains, containing containing a Val158Met mutation, commonly associated with the development of schizophrenia and other psychiatric disorders, are available on a congenic B6J background (Stock No. 032383) and a 129 coisogenic background (Stock No. 027993). The congenic B6J Val158Met strain shows behavioral phenotypes consistent with those seen in patients with schizophrenia and other psychiatric disorders.

Development

The Human COMT Val targeting construct was designed to replace the entire endogenous catechol-O-methyltransferase (Comt) coding region with human Comt sequence followed by a neomycin (neo) resistance cassette. This targeting construct was electroporated into 129Sv-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. Human COMT Val 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^{tm1(COMT)Xzho}
Name: targeted mutation 1, Xianjin Zhou
MGI accession ID: MGI:5661839
Generation method: Targeted
Attributes: Null/Knockout; Inserted expressed sequence
Marker symbol: Comt
Marker name: catechol-O-methyltransferase
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. Western blot analysis confirmed the absence of protein expression in the hippocampus and cortex.