B6.129P2-Axl^tm1Dgen/J

Stock number: 005777
Product name: Axl KO
Research areas: Apoptosis Research, Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Reproductive Biology Research, Research Tools, Virology Research

Description

These Axl KO mice may be useful in studies of innate immunity, autoimmunity, germ cell development and apoptosis. Axl is highly expressed by key cellular targets of ZIKA virus (ZIKV), and is proposed to promote viral entry in certain cell types (including non-Axl-expressing cells). Axl inhibition represents a potential approach for antiviral therapies.

Detailed description

This targeted mutant was created and characterized by Deltagen, Inc. View phenotypic data developed by Deltagen.

Briefly, a bacterial beta-galactosidase gene (lacZ) was inserted into the Axl locus such that the endogenous gene promoter drives lacZ expression. RNA transcripts are detectable in all tissues analyzed. lacZ expression is detectable in all tissues or organs analyzed. There were no significant differences detected in the homozygous mutant mice when compared with age- and gender-matched wildtype control mice.

In combination with mutations in other receptor tyrosine kinases, this strain may be useful in studies of innate immunity, autoimmunity, germ cell development and apoptosis.

The TAM receptors (Tyro3, Axl, and Mertk) are a family of receptor tyrosine kinases whose ligands (Gas6 and Protein S) bind to phosphatidylserine on the surface of apoptotic cells and enveloped viruses. Axl is highly expressed by key cellular targets of ZIKA virus (ZIKV) - including human radial glial cells, astrocytes, endothelial cells and microglia in developing human cortex, and by progenitor cells in developing retina (Nowakowski et al. 2016 Cell Stem Cell 18:591), as well as in subtypes of trophoblasts (Tabata et al. 2016 Cell Host Microb. 20:155). Research in 2017 identifies a dual role of Axl during ZIKV infection of human glial cells (astrocytes and microglia) - promoting viral entry and modulating innate immune responses - and suggests Axl inhibition may represent a potential target for antiviral therapies (Meertens et al. 2017 Cell Rep. 18:324).

Development

This Axl KO allele has a Lac0-SA-IRES-lacZ-Neo555G/Kan cassette replacing exons 1-11 of the AXL receptor tyrosine kinase (Axl) gene. Upon arrival at The Jackson Laboratory, these mice had been backcrossed at least six generations to C57BL/6 mice.

Allele

Symbol: Axl^tm1Dgen
Name: targeted mutation 1, Deltagen
MGI accession ID: MGI:3604510
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Axl
Marker name: AXL receptor tyrosine kinase
Chromosome: 7
Strain of origin: 129P2/OlaHsd
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: lacZ expression is detected in: brain, spinal cord, sciatic nerve, eyes, Harderian glands, thymus, spleen, lymph nodes, bone marrow, aorta, heart, lung, liver, gallbladder, pancreas, kidney, urinary bladder, trachea, larynx, esophagus, thyroid gland, parathyroid gland, pituitary gland, adrenal glands, salivary glands, tongue, skeletal muscle, skin, male and female reproductive systems. With strong expression detected in smooth muscle cells, blood vessels, capsules and connective tissue.
Molecular note: A bacterial lacZ gene was inserted into the gene such that the endogenous gene promoter drives expression of beta-galactosidase. RNA transcripts are detectable in all tissues analyzed. LacZ (beta-galactosidase) expression is detectable in all tissues or organs analyzed.