Targeted disruption of the
            <i>Kcnq1</i>
            gene produces a mouse model of Jervell and Lange– Nielsen Syndrome

Casimiro, Mathew C.; Knollmann, Björn C.; Ebert, Steven N.; Vary, James C.; Greene, Anne E.; Franz, Michael R.; Grinberg, Alexander; Huang, Song Lih; Pfeifer, Karl

doi:10.1073/pnas.041398998

Cited by 236 publications

(238 citation statements)

References 43 publications

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“…Mutations in both KCNQ1 and KCNE1 cause Jervell and Lange-Nielsen syndrome in humans (Neyroud et al 1997;Schulze-Bahr et al 1997), a syndrome associated with ventricular tachyarrhythmias of the heart and deafness. Knockout mouse models for both genes show a collapsed membranous labyrinth indicative of endolymph secretion failure and disruption of fluid homeostasis in the inner ear (Vetter et al 1996;Lee et al 2000;Casimiro et al 2001). A spontaneous mouse mutant, Punk Rocker, with a nonsense mutation in Kcne1 that results in a truncated protein, also shows an inner ear phenotype similar to the knockout mice .…”

Section: Genes That Affect Fluid Homeostasismentioning

confidence: 99%

Molecular Genetics of Vestibular Organ Development

Chang¹,

Cole²,

Cantos³

et al. 2004

The Vestibular System

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Section: Genes That Affect Fluid Homeostasismentioning

confidence: 99%

Molecular Genetics of Vestibular Organ Development

Chang¹,

Cole²,

Cantos³

et al. 2004

The Vestibular System

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“…In a recessive variant of this syndrome, JLNS, there is also deafness due to deficient endolymphatic circulation, reviewed in (Wang et al, 1998). In two studies, knockout mice lacking Kcnq1 exhibited deafness and loss of balance, with disruption of the inner ear anatomy due to insufficient endolymph Casimiro et al, 2001). This was the most obvious abnormality, but other features were observed.…”

Section: Imprinted Genes Expressedmentioning

confidence: 99%

Physiological functions of imprinted genes

Tycko

Morison

2002

Journal Cellular Physiology

290

203

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Genomic imprinting in gametogenesis marks a subset of mammalian genes for parent-of-origin-dependent monoallelic expression in the offspring. Embryological and classical genetic experiments in mice that uncovered the existence of genomic imprinting nearly two decades ago produced abnormalities of growth or behavior, without severe developmental malformations. Since then, the identification and manipulation of individual imprinted genes has continued to suggest that the diverse products of these genes are largely devoted to controlling pre-and post-natal growth, as well as brain function and behavior. Here, we review this evidence, and link our discussion to a website (http://www.otago.ac.nz/IGC) containing a comprehensive database of imprinted genes. Ultimately, these data will answer the long-debated question of whether there is a coherent biological rationale for imprinting.

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“…When coassembled with the regulatory accessory subunit KCNE1 (also known as minK and Isk), it forms the ''slow delayed rectifier'' (20,21). Mutations in KCNQ are responsible for an inherited birth defect that leads to cardiac long-QT arrhythmia (22), and for the hearing loss observed in Jervell and Lange-Nielsen Syndromes (23).…”

mentioning

confidence: 99%

Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells

Morokuma¹,

Blackiston²,

Adams³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

102

124

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Ion transporters, and the resulting voltage gradients and electric fields, have been implicated in embryonic development and regeneration. These biophysical signals are key physiological aspects of the microenvironment that epigenetically regulate stem and tumor cell behavior. Here, we identify a previously unrecognized function for KCNQ1, a potassium channel known to be involved in human Romano-Ward and Jervell-Lange-Nielsen syndromes when mutated. Misexpression of its modulatory wild-type ␤-subunit XKCNE1 in the Xenopus embryo resulted in a striking alteration of the behavior of one type of embryonic stem cell: the pigment cell lineage of the neural crest. Depolarization of embryonic cells by misexpression of KCNE1 non-cell-autonomously induced melanocytes to overproliferate, spread out, and become highly invasive of blood vessels, liver, gut, and neural tube, leading to a deeply hyperpigmented phenotype. This effect is mediated by the up-regulation of Sox10 and Slug genes, thus linking alterations in ion channel function to the control of migration, shape, and mitosis rates during embryonic morphogenesis. Taken together, these data identify a role for the KCNQ1 channel in regulating key cell behaviors and reveal the molecular identity of a biophysical switch, by means of which neoplastic-like properties can be conferred upon a specific embryonic stem cell subpopulation.cancer ͉ ion channel ͉ melanocyte ͉ neural crest ͉ KCNQ

show abstract

Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange– Nielsen Syndrome

Cited by 236 publications

References 43 publications

Molecular Genetics of Vestibular Organ Development

Molecular Genetics of Vestibular Organ Development

Physiological functions of imprinted genes

Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells

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