QTL analyses of temporal and intensity components of home-cage activity in KJR and C57BL/6J strains.

ABSTRACT

BACKGROUND: A variety of mouse strains exhibit diversity in spontaneous activity consistent with an important genetic contribution. To date, many studies have defined spontaneous home-cage activity as total distance or total counts of activity within a test period. However, spontaneous activity is, in fact, a composite of elements of 'temporal' and 'intensity' that is similar to 'velocity'. Here, we report on quantitative trait loci for different components of spontaneous activity, an important step towards dissection of the underlying genetic mechanisms. RESULTS: In the analysis of total home-cage activity (THA) after habituation in female mice, KJR strain exhibit higher activity than C57BL/6J (B6). In this study, THA was partitioned into two components active time (AT) was an index of the 'temporal element' of THA, average activity during active time (AA) was an index of 'intensity'. Correlation analysis using B6xKJR F2 female mice indicated that AA is a major component of THA, whereas AA and AT were associated to a lesser degree. To explore the genetic basis of the activity differences, we conducted quantitative trait loci (QTL) analysis on data of THA and its components, AT and AA. Three significant QTL affecting variation of different components of home cage activity were identified, two linked QTL Hylaq1 and Hylaq2 on Chr 2, and Hylaq3 on Chr 10. Chromosomal positions of these QTL were previously implicated in locomotor activity (Chr 2) or open-field ambulation (Chr 10). The results indicated that Hylaq1 influences AT, Hylaq2, AA, while Hylaq3 is associated with both AA and AT. CONCLUSION: Through this study, we found that variation in total home cage activity over a 3 day period is affected by variation in active time and intensity of activity. The latter two variables are distinct components of home cage activity with only partially overlapping genetic architecture.