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A B2 SINE insertion in the Comt1 gene (Comt1<sup>B2i</sup>) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains

Kember, RL and Fernandes, C and Tunbridge, EM and Liu, L and Payá-Cano, JL and Parsons, MJ and Schalkwyk, LC (2010) 'A B2 SINE insertion in the Comt1 gene (Comt1<sup>B2i</sup>) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains.' Genes, Brain and Behavior, 9 (8). 925 - 932. ISSN 1601-1848

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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 (Comt1B2i) 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. Comt1B2i 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 Comt1B2i 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 Comt1B2i (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. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 14 Nov 2014 17:00
Last Modified: 22 Jun 2021 11:15

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