Species: Mouse
Genes: Tardbp
Mutations: Tardp Q331K
Modification: Tardbp: Knock-In
Disease Relevance: Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
Strain Name: N/A
Genetic Background: C57BL/6J
Availability: Available through Pietro Fratta or Abraham Acevedo-Arozena

Summary

CRISPR/Cas9 was used to introduce the p.Q331K mutation into the mouse Tardp gene (Fratta et al., 2018). These mice can be used to study the effects of the p.Q331K mutation when TDP-43 is expressed at physiological levels, under the control of its natural regulatory elements.

Studies of tissues derived from these mice revealed that the p.Q331K mutation in TDP-43 results in a gain of splicing function, so that there is more exon skipping of specific “skiptic exons” (skipped exons that are normally constitutively expressed).

Modificaton Details

CRISPR/Cas9 was used to introduce the p.Q331K mutation into the mouse Tardp gene.

Phenotype Characterization

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References

Paper Citations

1. Fratta P, Sivakumar P, Humphrey J, Lo K, Ricketts T, Oliveira H, Brito-Armas JM, Kalmar B, Ule A, Yu Y, Birsa N, Bodo C, Collins T, Conicella AE, Mejia Maza A, Marrero-Gagliardi A, Stewart M, Mianne J, Corrochano S, Emmett W, Codner G, Groves M, Fukumura R, Gondo Y, Lythgoe M, Pauws E, Peskett E, Stanier P, Teboul L, Hallegger M, Calvo A, Chiò A, Isaacs AM, Fawzi NL, Wang E, Housman DE, Baralle F, Greensmith L, Buratti E, Plagnol V, Fisher EM, Acevedo-Arozena A. Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis. EMBO J. 2018 Jun 1;37(11) Epub 2018 May 15 PubMed.

External Citations

1. Pietro Fratta
2. Abraham Acevedo-Arozena

Further Reading

No Available Further Reading