| Allele Name | targeted mutation 2, John P Adelman |
| Allele Type | Targeted (Inserted expressed sequence) |
| Allele Synonym(s) | mSK2 tTAdeltaneo; SK2T |
| Gene Symbol and Name | Kcnn2, potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 |
| Gene Synonym(s) | |
| Promoter | tetO, tet operator, |
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| Expressed Gene | tTA, tetracycline-controlled transactivator, E. coli |
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| Site of Expression | In the absence of dox, homozygous mice exhibit enhanced SK channel-mediated restriction of glutamatergic activity in CA1 neurons, attenuated hippocampal synaptic plasticity, impaired spatial learning and memory in the Morris water maze, and impaired contextual and cued fear conditioning. |
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| Strain of Origin | 129S4/SvJae |
| Chromosome | 18 |
| Molecular Note | A genetic switch based on the tetracycline transactivator/tetracycline operator (tTA/tetO) system was inserted into the 5' untranslated region (5' UTR) of the targeted gene 40 nucleotides upstream of the initiator ATG. The switch, after in vivo excision of a selection cassette, comprises a tripartite adenovirus leader sequence (to enhance translation initiation efficiency) followed by the coding sequence for the tTA protein with SV40 and human growth hormone polyadenylation signals separated by a single loxP site; and five copies of the tetracycline operator (tetO), also called the tetracycline responsive element (TRE), joined to the cytomegalovirus (CMV) minimal promoter. In the absence of doxycycline (Dox), heterozygous mutant mice express 4.5-fold the wild-type level of Kcnn2 mRNA and 10-fold the wild-type level of Kcnn2 subunit protein, respectively assessed by quantitative and real-time PCR of whole-brain RNA and by immunoblot analysis of membrane proteins from whole brains. Administration of Dox reduces, but does not eliminate, expression from the mutant allele. |
| Mutations Made By | John Adelman, Vollum Inst. Oregon Health & Sci. Univ. |
