Goal 1: Promote Human Health

The CRISPER-Cas challenge: Need to re-phenotype KO animals?

Because traditional knock out models and CRISP/Cas models often show different phenotypes for the same gene deletion, do we need to re-phenotype hundreds/thousands of knock out animal models and revisit the conclusions of many studies based on using these animal models? This research may not appear very innovative but may be very important for drawing correct conclusions about gene functions and interactions - should NHLBI/NIH support re-phenotyping efforts?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Discovering differences in phenotypes may change many conclusions reported previously regarding gene functions and interactions.

Feasibility and challenges of addressing this CQ or CC

New methodologies for genetic editing are available
I recently saw at least of couple of presentations showing compelling evidence that KO mice generated with CRISPR (clustered regularly interspaced short palindromic repeat) and Cas (CRISPR-associated) had different phenotypes from the corresponding existing - and widely used - KO (same gene had been knocked-out) using previous methods. This was attributed to the non-specific modification introduced by previously used constructs/methods compared to the most recent precise genetic editing methods using with CRISPER-Cas.

Name of idea submitter and other team members who worked on this idea NHLBI Staff


-16 net votes
10 up votes
26 down votes
Idea No. 277