C57BL/6J-Tbk1^em8Lutzy

Stock number: 028123
Product name: Tbk1 N22D KI
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

This CRISPR/Cas9 generated Tbk1 N22D knock-in mutant of the Tbk1 gene carries a N22D knock in mutation (a single AAT -> GAT) in exon 6. This strain may be useful in studies related to inflammatory response regulation, autophagy, and frontotemporal dementia and/or amyotrophic lateral sclerosis 4.

Detailed description

This CRISPR/Cas9 generated mutant of the Tbk1 (TANK-binding kinase 1) carries a N22D point mutation, a single AAT -> GAT, in exon 6. The Tbk1 gene encodes a serine/threonine kinase that is involved in inflammatory response regulation and autophagy. Mutations in this gene are associated with frontotemporal dementia and/or amyotrophic lateral sclerosis 4. Homozygous mice are viable and fertile. As the mice are characterized, we will modify the strain description and add phenotype data.

Development

Plasmids encoding a single guide RNA designed to introduce a N22D point mutation into exon 6 of the Tbk1 gene and the cas9 nuclease were introduced into the cytoplasm C57BL/6J-derived fertilized eggs with well recognized pronuclei. Correctly targeted embryos were transferred to pseudopregnant females. Correctly targeted pups were identified by sequencing and PCR and further bred to C57BL/6J (Stock No. 000664) for 2 generations to develop the colony.

Allele

Symbol: Tbk1^em8Lutzy
Name: endonuclease-mediated mutation 8, Cathy Lutz
MGI accession ID: MGI:6295419
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Marker symbol: Tbk1
Marker name: TANK-binding kinase 1
Chromosome: 10
Strain of origin: C57BL/6J
Molecular note: CRISPR/Cas9 genome editing is used to introduce a AATto GAT resulting in an N22D amino acid substitution in exon 6. In humans, the N22D substitution is associated with amyotrophic lateral sclerosis.