Quantitative trait loci affecting the behavior of A/J and CBA/J intercross mice in the elevated plus maze

Abstract.

How allelic diversity affects neural mechanisms to produce behavioral variation is largely unknown. The elevated plus maze, consisting of open and closed arms, has been used as a model of behavioral variation in rodent exploration. Under dim illumination the nature of the sensory stimuli that influence arm choice is uncertain. Two inbred mouse strains, A/J (Tyr ^c /Tyr ^c , the albino phenotype, mutation in tyrosinase) with a strong preference for closed arm entry, and CBA/J (Pdeb ^rdl /Pdeb ^rdl , the retinal degeneration phenotype, mutation in the β-subunit of rod cGMP phosphodiesterase), with a weak preference for open arm entry, were studied under varying light. Because behavioral differences persist under red light, variation in light perception is not likely to fully account for variation in arm choice. To identify genetic factors influencing arm choice (100 × Open arm entries/Total arm entries) quantitative trait loci analyses (QTL) were performed on (A/J × CBA/J)F₂ mice. Two QTLs, one of which includes PDEB, were identified on Chr 5 (LOD > 10) and account for > 30% of the behavioral variation in arm preference. Tyr (Chr 7, 44 cM) was linked to closed arm entries but not arm preference, and is unlikely to be acting through a direct effect on light perception, because A/J arm entries were not affected by red light and there was no interaction with PDEB in the (A/J × CBA/J)F₂ mice. Whether the candidate QTLs on Chr 5 affect arm choice through an effect on light perception is unknown, but phenotypic differences between F₂ mice with retinal degeneration and CBA/J mice and F₂ mice with albinism and A/J mice suggest that factors other than light sensitivity contribute to arm preference in these two strains.