B6.129P2-Kif13b^{Gt(AF0005)Wtsi}/AhcJ

Stock number: 034596
Product name: KIF13BΔCG
Research areas: Cardiovascular Research, Cell Biology Research, Hematological Research, Neurobiology Research

Description

KIF13BΔCG mice have a gene trap vector, containing a β-galactosidase-neomycin (β-geo) gene, inserted downstream of exon 38 of the kinesin family member 13B (Kif13b) gene. This strain may be useful for studying KIF13B regulation of LRP1 and its role in metabolism, cell polarity, and development.

Detailed description

KIF13BΔCG mice have a gene trap vector, containing a β-galactosidase-neomycin (β-geo) gene, inserted downstream of exon 38, encoding the C-terminus CAP-Gly domain, of the kinesin family member 13B (Kif13b) gene. Kif13b encodes a kinesin-3 family motor involved in the reorganization of the cortical cytoskeleton. It regulates axon formation by promoting the formation of extra axons. KIF13B is involved in intracellular trafficking of VEGFR2 to the plasma membrane to regulate angiogenesis, binding to Disheveled to induce planar cell polarity, sorting and trafficking of retrograde BMP signaling in motor neurons, regulating peripheral and central nervous system myelination, and cilia-dependent Sonic hedgehog signaling. This gene may be functionally important for the intracellular trafficking of MAGUKs (membrane associated guanylate kinase homologues).

This KIF13BΔCG mutation results in the removal of the C-terminus of the gene, including the Cytoskeleton-Associated Protein Glycine-rich (CAP-Gly) domain, which is the domain that distinguishes this gene from its homolog KIF13A. This CAP-Gly domain region of KIF13B selectively regulates LDL-receptor Related Protein 1 (LRP1)-mediated lipoprotein endocytosis. The resulting protein is truncated. KIF13BΔCG mice show a modest elevation of serum cholesterol phenotype similar to the KIF13B full-length knock-out (FLKO) mouse line, with no elevation of either serum cholesterol or plasma factor VIII.

When KIF13BΔCG mice are bred to KIF13A FLKO full-length knock-out mice (Stock No. 034597), double knock-out (DKO) mice exhibit post-natal lethality during day 1 due to an inability to suckle, probably due to craniofacial abnormalities. They did not appear to have a clefting phenotype.

Development

A gene trap vector (pGT0lxr) containing a β-galactosidase-neomycin (β-geo) gene was electroporated into 129P2/OlaHsd-derived embryonic stem (ES) cells. An ES cell line (AF0005) in which the gene-trap vector was inserted downstream of exon 38 of the kinesin family member 13B (Kif13b) gene was identified by PCR and western blot. This mutation results in the removal of the C-terminus of the gene, including the Cytoskeleton-Associated Protein Glycine-rich (CAP-Gly) domain. Correctly targeted ES cells were injected into blastocysts and resulting KIF13BΔCG chimeric mice were backcrossed 20 generations to C57BL/6J mice (Stock No. 000664). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Kif13b^{Gt(AF0005)Wtsi}
Name: gene trap AF0005, Wellcome Trust Sanger Institute
MGI accession ID: MGI:3876683
Generation method: Gene trapped
Attributes: Reporter; Null/Knockout
Synonyms: KIF13BdeltaCG
Marker symbol: Kif13b
Marker name: kinesin family member 13B
Marker synonyms: 5330429L19Rik; C130021D12Rik; GAKIN; N-3 kinesin
Chromosome: 14
Strain of origin: 129P2/OlaHsd
Molecular note: The gene-trap vector (beta-geo) is inserted downstream of exon 38. The mutation results in the removal of the C-terminus of the gene, including a proline-rich domain and the Cytoskeleton-Associated Protein Glycine-rich (CAP-Gly) domain (amino acids 1521-1843). The expression of truncated protein is not identifiable by Western blotting, but can be identified by LacZ staining of embryos and mouse embryonic fibroblasts.