Generation and analysis of innovative genomically humanized knockin <i>SOD1</i>, <i>TARDBP</i> (TDP-43), and <i>FUS</i> mouse models.

ABSTRACT: Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a fatal neurodegenerative disorder, and continued innovation is needed for improved understanding and for developing therapeutics. We have created next-generation genomically humanized knockin mouse models, by replacing the mouse genomic region of Sod1, Tardbp (TDP-43), and Fus, with their human orthologs, preserving human protein biochemistry and splicing with exons and introns intact. We establish a new standard of large knockin allele quality control, demonstrating the utility of indirect capture for enrichment of a genomic region of interest followed by Oxford Nanopore sequencing. Extensive analysis shows that homozygous humanized animals only express human protein at endogenous levels. Chara

SUBMITTER: Devoy A 

PROVIDER: S-EPMC8710557 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature