C57BL/6J-Tbk1^em6Lutzy/J

Stock number: 027983
Product name: Tbk1 R228H KI
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

This CRISPR/Cas9 generated knock-in Tbk1 R228H knock-in mutant of the Tbk1 gene carries a CGG->CAT codon change, resulting in the R228H point mutation. This strain may be useful in studies related to inflammatory response regulation, autophagy, and frontotemporal dementia and/or amyotrophic lateral sclerosis 4.

Detailed description

CRISPR/cas9 endonuclease mediated genome editing of the Tbk1, TANK-binding kinase 1, gene was used to introduce a CGG->CAT codon change (R228H point mutation). The targeted Tbk1 gene encodes a serine/threonine kinase that is involved in inflammatory response regulation and autophagy. Mutations in this gene have been 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

CRISPR/cas9 endonuclease mediated R228H knock-in point mutation of Tbk1. Plasmids encoding a signal guide RNA designed to introduce the CGG->CAT codon change in 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^em6Lutzy
Name: endonuclease-mediated mutation 6, Cathy Lutz
MGI accession ID: MGI:6295381
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Synonyms: Tbk1^R228H
Marker symbol: Tbk1
Marker name: TANK-binding kinase 1
Marker synonyms: 1200008B05Rik; FTDALS4; IIAE8; NAK; T2K
Chromosome: 10
Strain of origin: C57BL/6J
Molecular note: CRISPR/cas9 genome editing is used to introduce a CGG to CAT codon change resulting in the R228H amino acid substitution. In humans, the R228H substitution is associated with amyotrophic lateral sclerosis.