title: Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene.
abstract: 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 (Clic1(FN)) allele, followed by Clic1 knock-out (Clic1(-/-)) mice by crossing Clic1(FN) allele with TNAP-cre 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 P2Y(12) receptor signaling.
authors.affiliation: St. Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Min Ru
authors.initials: MR
authors.lastname: Qiu
authors.forename: Lele
authors.initials: L
authors.lastname: Jiang
authors.forename: Klaus I
authors.initials: KI
authors.lastname: Matthaei
authors.forename: Simone M
authors.initials: SM
authors.lastname: Schoenwaelder
authors.forename: Tamara
authors.initials: T
authors.lastname: Kuffner
authors.forename: Pierre
authors.initials: P
authors.lastname: Mangin
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Joseph
authors.forename: Joyce
authors.initials: J
authors.lastname: Low
authors.forename: David
authors.initials: D
authors.lastname: Connor
authors.forename: Stella M
authors.initials: SM
authors.lastname: Valenzuela
authors.forename: Paul M G
authors.initials: PM
authors.lastname: Curmi
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Brown
authors.forename: Martyn
authors.initials: M
authors.lastname: Mahaut-Smith
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Jackson
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
mesh_terms: D000483:Alleles; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D018118:Chloride Channels / Q000235:genetics*; D003433:Crosses, Genetic; D017353:Gene Deletion; D018390:Gene Targeting / Q000379:methods*; D005818:Genetic Engineering; D006470:Hemorrhage; D006579:Heterozygote; D006720:Homozygote; D007150:Immunohistochemistry; D019426:Integrases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D011995:Recombination, Genetic
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels; C045073:Cre recombinase; D019426:Integrases