A B2 SINE insertion in the Comt1 gene (Comt1(B2i)) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains.
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 nucleoti...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1826293371995422720 |
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| author | Kember, R Fernandes, C Tunbridge, E Liu, L Payá-Cano, J Parsons, M Schalkwyk, L |
| author_facet | Kember, R Fernandes, C Tunbridge, E Liu, L Payá-Cano, J Parsons, M Schalkwyk, L |
| author_sort | Kember, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:29:05Z |
| format | Journal article |
| id | oxford-uuid:ba0fc5eb-c049-4304-a39f-c98a01f55f86 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:29:05Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:ba0fc5eb-c049-4304-a39f-c98a01f55f862022-03-27T05:07:22ZA B2 SINE insertion in the Comt1 gene (Comt1(B2i)) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ba0fc5eb-c049-4304-a39f-c98a01f55f86EnglishSymplectic Elements at Oxford2010Kember, RFernandes, CTunbridge, ELiu, LPayá-Cano, JParsons, MSchalkwyk, LCatechol-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. |
| spellingShingle | Kember, R Fernandes, C Tunbridge, E Liu, L Payá-Cano, J Parsons, M Schalkwyk, L A B2 SINE insertion in the Comt1 gene (Comt1(B2i)) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains. |
| title | A B2 SINE insertion in the Comt1 gene (Comt1(B2i)) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains. |
| title_full | A B2 SINE insertion in the Comt1 gene (Comt1(B2i)) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains. |
| title_fullStr | A B2 SINE insertion in the Comt1 gene (Comt1(B2i)) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains. |
| title_full_unstemmed | A B2 SINE insertion in the Comt1 gene (Comt1(B2i)) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains. |
| title_short | A B2 SINE insertion in the Comt1 gene (Comt1(B2i)) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains. |
| title_sort | b2 sine insertion in the comt1 gene comt1 b2i results in an overexpressing behavior modifying allele present in classical inbred mouse strains |
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