A high through-put reverse genetic screen identifies two genes involved in remote memory in mice

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Memory formation involves synaptic, transcriptional, and translational mechanisms.
• Molecular mechanisms of later memory stages, particularly remote memory (7-day memory), are largely unknown.

Purpose of the Study:

• To identify genes crucial for the formation and consolidation of remote memory.
• To explore the utility of reverse genetic screens in discovering genes involved in complex cognitive processes.

Main Methods:

• A reverse genetic screen of 54 randomly selected mouse strains with known mutations.
• Secondary screens to validate the specific impact of identified mutations on remote memory.

Main Results:

• Identified 4 putative remote memory mutant strains from the initial screen.
• Confirmed that mutations in integrin beta2 (Itgbeta2) and steryl-O-acyl transferase 1 (Soat1) specifically impair remote memory.
• 11 additional mutant strains showed other abnormal profiles.

Conclusions:

• Identified the first genes, Itgbeta2 and Soat1, required for remote memory.
• Reverse genetic screens of targeted mutants are an efficient strategy for identifying molecular requirements for remote memory.