Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene

Min Ru Qiu, Lele Jiang, Klaus I. Matthaei, Simone M. Schoenwaelder, Tamara Kuffner, Pierre Mangin, Joanne E. Joseph, Joyce Low, David Connor, Stella M. Valenzuela, Paul M.G. Curmi, Louise J. Brown, Martyn Mahaut-Smith, Shaun P. Jackson, Samuel N. Breit

    Research output: Contribution to journalArticlepeer-review

    34 Citations (Scopus)

    Abstract

    Summary: CLIC1 belongs to a family of highly conserved and widely expressed intracellular chloride ion channel proteins existing in both soluble and membrane integrated forms. To study the physiological and biological role of CLIC1 in vivo, we undertook conditional gene targeting to engineer Clic1 gene knock-out mice. This represents creation of the first gene knock-out of a vertebrate CLIC protein family member. We first generated a Clic1 Knock-in (Clic1FN) allele, followed by Clic1 knockout (Clic1-/-) mice by crossing Clic1FN allele with TNAPcre mice, resulting in germline gene deletion through Cre-mediated recombination. Mice heterozygous or homozygous for these alleles are viable and fertile and appear normal. However, Clic1-/- mice show a mild platelet dysfunction characterized by prolonged bleeding times and decreased platelet activation in response to adenosine diphosphate stimulation linked to P2Y12 receptor signaling.

    Original languageEnglish
    Pages (from-to)127-136
    Number of pages10
    JournalGenesis (United States)
    Volume48
    Issue number2
    DOIs
    Publication statusPublished - Feb 2010

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