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UCSF Team Reports on microRNA Knockout Mouse Resource

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Researchers from the University of California, San Francisco, last month reported on the assembly of a publicly available library of conditional, reporter-tagged knockout-first mice for certain evolutionarily conserved microRNAs.

“From cancer to diabetes to immune diseases of unknown genetic nature, the project has generated a high-value resource for people out there who want to test specific ideas related to any human disease or developmental disorder,” UCSF researcher Michael McManus, who led the research, said in a statement.

In order to develop the resource, called miRKO, McManus and his colleagues generated a “battery of novel miRNA reporter and conditional knockout mouse lines, and collected limited in vivo expression data from a subset of targeted lines,” they wrote in a report in Cell. “Investigators can use this resource to explore the phenotypic consequences of disruption of miRNAs.”

Specifically, they generated 162 miRNA targeting vectors, 64 targeted embryonic stem cell lines, and 46 germline-transmitted miRNA knockout mice, according to the paper. “In vivo lacZ reporter analysis in 18 lines revealed highly tissue-specific expression patterns and their miRNA expression profiling matched closely with published expression data. Most miRNA knockout mice tested were viable, supporting a mechanism by which miRNAs act redundantly with other miRNAs or other pathways.”

According to the Cell paper, the team is continuing to generate additional data. The resulting resources, including targeting vectors, embryonic stem cell lines, and mice, will be available to researchers through the University of California, Davis, Knockout Mouse Project Repository and through the Jackson Laboratory.

“The active pipeline can be viewed online at the miRKO database, where each miRNA can be tracked from plasmid production stage to the generation of mice and the deposition of mice to the Jackson Laboratory,” McManus and his team added in Cell. “Vector maps, ES cell data, high-resolution reporter expression data, and protocols are available for download.”

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