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.
Cathleen Lutz, The Jackson Laboratory
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.
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 Name||endonuclease-mediated mutation 8, Cathy Lutz|
|Allele Type||Endonuclease-mediated (Humanized sequence)|
|Gene Symbol and Name||Tbk1, TANK-binding kinase 1|
|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.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Tbk1 N22D KI mouse strain in a publication, please cite the originating article(s) and include JAX stock #028123 in your Materials and Methods section.