Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene.
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.
Qiu
Min Ru
MR
St. Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
Jiang
Lele
L
Matthaei
Klaus I
KI
Schoenwaelder
Simone M
SM
Kuffner
Tamara
T
Mangin
Pierre
P
Joseph
Joanne E
JE
Low
Joyce
J
Connor
David
D
Valenzuela
Stella M
SM
Curmi
Paul M G
PM
Brown
Louise J
LJ
Mahaut-Smith
Martyn
M
Jackson
Shaun P
SP
Breit
Samuel N
SN
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
C086321:CLC-1 channel; D018118:Chloride Channels; C045073:Cre recombinase; D019426:Integrases