The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

Kcnq1  -  potassium voltage-gated channel, subfamily...

Mus musculus

Synonyms: AW559127, IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1, KQT-like 1, KVLQT1, Kcna9, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of Kcnq1

  • Sequence-based structural features between Kvlqt1 and Tapa1 on mouse chromosome 7F4/F5 corresponding to the Beckwith-Wiedemann syndrome region on human 11p15.5: long-stretches of unusually well conserved intronic sequences of kvlqt1 between mouse and human [1].
  • Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange-Nielsen Syndrome [2].
  • Metaplasia, dysplasia and pre-malignant adenomatous hyperplasia of the stomach have been observed in these Kcnq1 mutant mice, also independent of infection [3].
  • Here, we present the characterization of two mouse lines carrying mutant alleles of the gene encoding the Kcnq1 potassium channel, which very rapidly establish chronic gastritis in a pathogen-exposed environment [3].
  • Thus, Kcnq1 mutant mice are a powerful new tool for investigating the connection between acid balance, Helicobacter infection and mucin disruption in the progression to gastric cancer [3].
 

High impact information on Kcnq1

  • Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes [4].
  • The KvDMR, which maps within intron 10 of Kcnq1, contains the promoter for a paternally expressed, noncoding, antisense transcript, Kcnq1ot1 [5].
  • Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice [6].
  • Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear [6].
  • Behavioral analysis revealed that the Kcnq1(-/-) mice are deaf and exhibit a shaker/waltzer phenotype [2].
 

Biological context of Kcnq1

  • Parallel to the loss of antisense transcription, the loss of silencing of the flanking reporter genes was observed, suggesting that NF-Y-mediated Kcnq1ot1 transcription is critical in the bidirectional silencing process of the Kcnq1 ICR [7].
  • The chromosomal localization on distal chromosome 7 places it in a cluster of imprinted genes, flanked by the previously described Tapa1 and Kcnq1 genes [8].
  • To elucidate whether the Kcnq1ot1 RNA plays a role in the bidirectional silencing activity of the Kcnq1 ICR, we have characterized factor binding sites by genomic footprinting and tested the functional consequence of various deletions of these binding sites in an episome-based system [9].
  • 5. Our findings show that the dynamics during preimplantation development of gene inactivation and acquisition of repressive histone marks in ubiquitously imprinted genes of the Kcnq1 domain are very similar to those of imprinted X inactivation [10].
  • Targeted point mutagenesis of mouse Kcnq1: phenotypic analysis of mice with point mutations that cause Romano-Ward syndrome in humans [11].
 

Anatomical context of Kcnq1

  • Histological analysis of the inner ear structures of Kcnq1(-/-) mice revealed gross morphological anomalies because of the drastic reduction in the volume of endolymph [2].
  • Coexpression of both alpha-subunits is observed in a wide variety of organs, such as heart and the skeletal muscle, whereas others display unique Kcnq1 or Knch2 expression [12].
  • METHODS: Hearing thresholds were measured in three Kcnq1 knockout mice, two heterozygous mice, and one wild-type mouse by auditory brainstem response recordings using clicks, after which the temporal bones were removed [13].
  • Mouse Kvlqt1 is strongly expressed in heart, lung, gut, kidney and uterus [14].
  • In human, the gene is imprinted in most fetal tissues except the heart, and KVLQT1 is part of a 1-Mb cluster of imprinted genes on human chromosome 11p15 [15].
 

Associations of Kcnq1 with chemical compounds

  • Nicotine induces a long QT phenotype in Kcnq1-deficient mouse hearts [16].
  • Similar findings were obtained when the hearts were challenged with either epinephrine or isoproterenol (0.1 microM each), thereby suggesting that sympathetic stimulation drives the long QT phenotype in Kcnq1-deficient hearts [16].
  • Examination of embryonic, neonatal, and postnatal tissues revealed that Kvlqt1 is imprinted in mouse early embryos, in both female 129 x male CS and female CS x male 129 offspring, with preferential expression of the maternal allele, like the human homologue [15].
 

Other interactions of Kcnq1

  • Lit1 is an antisense-transcript of Kvlqt1 and paternally expressed and maternally methylated throughout the developmental stage [1].
  • Imprinting of Igf2r, Kcnq1, Gt12, and Dlk1 varied among individuals [17].
  • Our results demonstrate that Kcnq1 and Kcnh2 are widely distributed [12].
  • The imprinted gene cluster on mouse distal chromosome 7 contains a differentially methylated CpG island that maps within the Kcnq1 gene that has been shown to be required for the imprinting of multiple genes [18].
 

Analytical, diagnostic and therapeutic context of Kcnq1

  • Together, these data suggest that Kcnq1(-/-) mice are a potentially valuable animal model of JLNS [2].
  • No significant differences in QT or any other ECG parameters were observed in Kcnq1+/+ versus Kcnq1-/- hearts at baseline [16].

References

  1. Sequence-based structural features between Kvlqt1 and Tapa1 on mouse chromosome 7F4/F5 corresponding to the Beckwith-Wiedemann syndrome region on human 11p15.5: long-stretches of unusually well conserved intronic sequences of kvlqt1 between mouse and human. Yatsuki, H., Watanabe, H., Hattori, M., Joh, K., Soejima, H., Komoda, H., Xin, Z., Zhu, X., Higashimoto, K., Nishimura, M., Kuratomi, S., Sasaki, H., Sakaki, Y., Mukai, T. DNA Res. (2000) [Pubmed]
  2. Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange-Nielsen Syndrome. Casimiro, M.C., Knollmann, B.C., Ebert, S.N., Vary, J.C., Greene, A.E., Franz, M.R., Grinberg, A., Huang, S.P., Pfeifer, K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  3. Heightened susceptibility to chronic gastritis, hyperplasia and metaplasia in Kcnq1 mutant mice. Elso, C.M., Lu, X., Culiat, C.T., Rutledge, J.C., Cacheiro, N.L., Generoso, W.M., Stubbs, L.J. Hum. Mol. Genet. (2004) [Pubmed]
  4. Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes. Umlauf, D., Goto, Y., Cao, R., Cerqueira, F., Wagschal, A., Zhang, Y., Feil, R. Nat. Genet. (2004) [Pubmed]
  5. Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Mancini-Dinardo, D., Steele, S.J., Levorse, J.M., Ingram, R.S., Tilghman, S.M. Genes Dev. (2006) [Pubmed]
  6. Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice. Lee, M.P., Ravenel, J.D., Hu, R.J., Lustig, L.R., Tomaselli, G., Berger, R.D., Brandenburg, S.A., Litzi, T.J., Bunton, T.E., Limb, C., Francis, H., Gorelikow, M., Gu, H., Washington, K., Argani, P., Goldenring, J.R., Coffey, R.J., Feinberg, A.P. J. Clin. Invest. (2000) [Pubmed]
  7. NF-Y regulates the antisense promoter, bidirectional silencing, and differential epigenetic marks of the Kcnq1 imprinting control region. Pandey, R.R., Ceribelli, M., Singh, P.B., Ericsson, J., Mantovani, R., Kanduri, C. J. Biol. Chem. (2004) [Pubmed]
  8. Mtr1, a novel biallelically expressed gene in the center of the mouse distal chromosome 7 imprinting cluster, is a member of the Trp gene family. Enklaar, T., Esswein, M., Oswald, M., Hilbert, K., Winterpacht, A., Higgins, M., Zabel, B., Prawitt, D. Genomics (2000) [Pubmed]
  9. An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region. Thakur, N., Tiwari, V.K., Thomassin, H., Pandey, R.R., Kanduri, M., Göndör, A., Grange, T., Ohlsson, R., Kanduri, C. Mol. Cell. Biol. (2004) [Pubmed]
  10. Epigenetic dynamics of the Kcnq1 imprinted domain in the early embryo. Lewis, A., Green, K., Dawson, C., Redrup, L., Huynh, K.D., Lee, J.T., Hemberger, M., Reik, W. Development (2006) [Pubmed]
  11. Targeted point mutagenesis of mouse Kcnq1: phenotypic analysis of mice with point mutations that cause Romano-Ward syndrome in humans. Casimiro, M.C., Knollmann, B.C., Yamoah, E.N., Nie, L., Vary, J.C., Sirenko, S.G., Greene, A.E., Grinberg, A., Huang, S.P., Ebert, S.N., Pfeifer, K. Genomics (2004) [Pubmed]
  12. Protein distribution of Kcnq1, Kcnh2, and Kcne3 potassium channel subunits during mouse embryonic development. de Castro, M.P., Aránega, A., Franco, D. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology. (2006) [Pubmed]
  13. Inner ear abnormalities in a Kcnq1 (Kvlqt1) knockout mouse: a model of Jervell and Lange-Nielsen syndrome. Rivas, A., Francis, H.W. Otol. Neurotol. (2005) [Pubmed]
  14. Imprinting of mouse Kvlqt1 is developmentally regulated. Gould, T.D., Pfeifer, K. Hum. Mol. Genet. (1998) [Pubmed]
  15. Strain-dependent developmental relaxation of imprinting of an endogenous mouse gene, Kvlqt1. Jiang, S., Hemann, M.A., Lee, M.P., Feinberg, A.P. Genomics (1998) [Pubmed]
  16. Nicotine induces a long QT phenotype in Kcnq1-deficient mouse hearts. Tosaka, T., Casimiro, M.C., Rong, Q., Tella, S., Oh, M., Katchman, A.N., Pezzullo, J.C., Pfeifer, K., Ebert, S.N. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  17. Increased plasticity of genomic imprinting of Dlk1 in brain is due to genetic and epigenetic factors. Croteau, S., Roquis, D., Charron, M.C., Frappier, D., Yavin, D., Loredo-Osti, J.C., Hudson, T.J., Naumova, A.K. Mamm. Genome (2005) [Pubmed]
  18. A differentially methylated region within the gene Kcnq1 functions as an imprinted promoter and silencer. Mancini-DiNardo, D., Steele, S.J., Ingram, R.S., Tilghman, S.M. Hum. Mol. Genet. (2003) [Pubmed]
 
WikiGenes - Universities