C57BL/6J-Tardbp^em1Rhbr/J

Stock number: 031345
Product name: TDP43 Q331K
Research areas: Developmental Biology Research, Neurobiology Research

Description

This CRISPR/Cas9 generated mutant of the Tardbp gene carries a Q331K point mutation making this strain useful when studying the ALS/FTD (amyotrophic lateral sclerosis [Lou Gehrig's disease] / frontotemporal dementia [frontotemporal lobar degeneration]), including progressive motor deficits in conjunction with neuromuscular junction abnormalities.

Detailed description

CRISPR/cas9 endonuclease mediated genome editing of the Tardbp (TAR DNA binding protein) gene was used to introduce a Q331K point mutation. The human TDP-43 encodes a ubiquinated, DNA/RNA-binding protein localized to the nucleus of cells. TDP-43 mutations in the amyloidogenic core region (residues 311-360) and the glycine-rich, flexible C-terminal region are associated with the development of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) and frontotemporal dementia (FTD or frontotemporal lobar degeneration). Homozygous mice are viable and fertile. These mice have a mild phenotype characterized by cognitive dysfunction and behavioral changes such as reduced walking and hanging, and increased rearing and eating by hand. Homozygous male mice show an increased reduction in walking over females, and homozygous males are born at a lower Mendelian frequency than females.

Development

Plasmids encoding a signal guide RNA designed to introduce a 1 bp base pair mutation (C>A) resulting in a Q331K point mutation in the Tardbp (TAR DNA binding protein) 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 mice to develop the colony. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (Stock No. 000664) oocytes.

Allele

Symbol: Tardbp^em1Rhbr
Name: endonuclease-mediated mutation 1, Robert Brown Jr
MGI accession ID: MGI:6157626
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Synonyms: TDP-43^Q331K
Marker symbol: Tardbp
Marker name: TAR DNA binding protein
Marker synonyms: 1190002A23Rik; ALS10; Tdp43; TDP-43
Chromosome: 4
Strain of origin: C57BL/6J
Molecular note: CRISPR/Cas9 methodologies were used to introduce a 1 bp base pair mutation (C>A) resulting in a Q331K point mutation. The Q331K mutation is associated with Amyotrophic Lateral Sclerosis.