C57BL/6N-Arhgef3^{tm1(KOMP)Wtsi}/DkrsJ

Stock number: 028838
Product name: Arhgef3 KO
Research areas: Hematological Research

Description

Arhgef3 knock-out mice lack exons 5-7 of the Rho guanine nucleotide exchange factor (GEF) 3 (Arhgef3) gene, and is useful when studying megakaryocyte and platelet function.

Detailed description

Arhgef3 knock-out mice have a cassette, including a lacZ sequence, replacing exons 5-7 of the Rho guanine nucleotide exchange factor (GEF) 3 (Arhgef3) gene. GEF3, also known as the Exchange Factor Found in Platelets, Leukemic, and Neuronal tissues, regulates the switch of Rho GTPase from the inactive GDP-bound state to the active GTP-bound state. In heterozygotes, ARHGEF3 is expressed, and lacZ staining is evident, in mature megakaryocytes. Arhgef3 KO mice have larger platelets as compared to controls, with no effect on platelet number or function. In response to antibody-mediated platelet depletion, Arhgef3 KO mice have a small delay in platelet recovery. Megakaryocyte maturation is normal. ARHGEF3 may play a more prominent role during megakaryocyte development and platelet activation in humans.

Development

The L1L2_Bact_P cassette was inserted at a position on Chromosome 14, resulting in a 2098 bp deletion starting at position 27384120 and ending at position 27386218, including exons 5-7 of the Rho guanine nucleotide exchange factor (GEF) 3 (Arhgef3) gene. The cassette is composed of an FRT site followed by En2SA (mouse engrailed 2 gene splice acceptor), IRES-lacZ sequence and a loxP site. This first loxP site is followed by a neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. The construct was introduced into C57BL/6N-A^tm1Brd-derived JM8A3.N1 embryonic stem (ES) cells, and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were bred together. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304). The A^tm1Brd allele was subsequently bred out of the colony.

Allele

Symbol: Arhgef3^{tm1(KOMP)Wtsi}
Name: targeted mutation 1, Wellcome Trust Sanger Institute
MGI accession ID: MGI:4419295
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Arhgef3
Marker name: Rho guanine nucleotide exchange factor (GEF) 3
Chromosome: 14
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: The insertion of the L1L2_Bact_P cassette created a deletion of size 2098 starting at position 27384120 and ending at position 27386218 of Chromosome 14 (Genome Build GRCm38). This deletion results in the removal of functionally critical exon(s). The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by a neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site.