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Brain Region-Specific Expression of Genes Mapped within Quantitative Trait Loci for Behavioral Responsiveness to Acute Stress in Fisher 344 and Wistar Kyoto Male Rats (Postprint)

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Journal Article - Open Access

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Northwestern University Chicago United States

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Acute stress responsiveness is a quantitative trait that varies in severity from one individual to another however, the genetic component underlying the individual variation is largely unknown. Fischer 344 F344 and Wistar Kyoto WKY rat strains show large differences in behavioral responsiveness to acute stress, such as freezing behavior in response to foot-shock during the conditioning phase of contextual fear conditioning CFC. Quantitative trait loci QTL have been identified for behavioral responsiveness to acute stress in the defensive burying DB and open field test OFT from a reciprocal F2 cross of F344 and WKY rat strains. These included a significant QTL on chromosome 6 Stresp10. Here, we hypothesized that the Stresp10 region harbors genes with sequence variations that contribute to differences in multiple behavioral response phenotypes between the F344 and WKY rat strains. To test this hypothesis, first we identified differentially expressed genes within the Stresp10 QTL in the hippocampus, amygdala, and frontal cortex of F344 and WKY male rats using genome-wide microarray analyses. Genes with both expression differences and non-synonymous sequence variations in their coding regions were considered candidate quantitative trait genes QTGs. As a proof-of-concept, the F344.WKY-Stresp10 congenic strain was generated with the Stresp10 WKY donor region into the F344 recipient strain. This congenic strain showed behavioral phenotypes similar to those of WKYs. Expression patterns of Gpatch11 G-patch domain containing 11, Cdkl4 Cyclin dependent kinase like 4, and Drc1 Dynein regulatory complex subunit 1 paralleled that of WKY in the F344.WKY-Stresp10 strain matching the behavioral profiles of WKY as opposed to F344 parental strains. We propose that these genes are candidate QTGs for behavioral responsiveness to acute stress.

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