title: A B2 SINE insertion in the Comt1 gene (Comt1(B2i)) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains.
abstract: Catechol-O-methyltransferase (COMT) is a key enzyme for dopamine catabolism and COMT is a candidate gene for human psychiatric disorders. In mouse it is located on chromosome 16 in a large genomic region of extremely low variation among the classical inbred strains, with no confirmed single nucleotide polymorphisms (SNPs) between strains C57BL/6J and DBA/2J within a 600-kB window. We found a B2 SINE in the 3' untranslated region (UTR) of Comt1 which is present in C57BL/6J (Comt1(B2i)) and other strains including 129 (multiple sublines), but is not found in DBA/2J (Comt1(+)) and many other strains including wild-derived Mus domesticus, M. musculus, M. molossinus, M.castaneus and M. spretus. Comt1(B2i) is absent in strains closely related to C57BL/6, such as C57L and C57BR, indicating that it was polymorphic in the cross that gave rise to these strains. The strain distribution of Comt1(B2i) indicates a likely origin of the allele in the parental Lathrop stock. A stringent association test, using 670 highly outbred mice (Boulder Heterogeneous Stock), indicates that this insertion allele may be responsible for a difference in behavior related to exploration. Gene expression differences at the mRNA and enzyme activity level (1.7-fold relative to wild type) indicate a mechanism for this behavioral effect. Taken together, these findings show that Comt1(B2i) (a B2 SINE insertion) results in a relatively modest difference in Comt1 expression and enzyme activity (comparable to the human Val-Met polymorphism) which has a demonstrable behavioral phenotype across a variety of outbred genetic backgrounds.
authors.affiliation: Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London, UK.
authors.forename: R L
authors.initials: RL
authors.lastname: Kember
authors.forename: C
authors.initials: C
authors.lastname: Fernandes
authors.forename: E M
authors.initials: EM
authors.lastname: Tunbridge
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: J L
authors.initials: JL
authors.lastname: Payá-Cano
authors.forename: M J
authors.initials: MJ
authors.lastname: Parsons
authors.forename: L C
authors.initials: LC
authors.lastname: Schalkwyk
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001483:Base Sequence; D001522:Behavior, Animal / Q000502:physiology*; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity
chemical_list: D012333:RNA, Messenger; D002394:Catechol O-Methyltransferase