Open AccessA B2 SINE insertion in the Comt1 gene ( Comt1 B2i ) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains
Author(s) -
Kember R. L.,
Fernandes C.,
Tunbridge E. M.,
Liu L.,
PayáCano J. L.,
Parsons M. J.,
Schalkwyk L. C.
Publication year - 2010
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2010.00614.x
Subject(s) - allele , genetics , gene , sine , biology , inbred strain , physics , microbiology and biotechnology , mathematics , geometry
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.