Lightfoot JT, Turner MJ, Knab AK, Jedlicka AE, Oshimura T, Marzec J, Gladwell W, Leamy LJ, Kleeberger SR. Quantitative trait loci associated with maximal exercise endurance in mice. J Appl Physiol 103: 105-110, 2007. First published April 5, 2007 doi:10.1152/japplphysiol.01328.2006.-The role of genetics in the determination of maximal exercise endurance is unclear. Six-to nine-week-old F2 mice (n ϭ 99; 60 female, 39 male), derived from an intercross of two inbred strains that had previously been phenotyped as having high maximal exercise endurance (Balb/cJ) and low maximal exercise endurance (DBA/2J), were treadmill tested to estimate exercise endurance. Selective genotyping of the F2 cohort (n ϭ 12 high exercise endurance; n ϭ 12 low exercise endurance) identified a significant quantitative trait locus (QTL) on chromosome X (53.7 cM, DXMit121) in the entire cohort and a suggestive QTL on chromosome 8 (36.1 cM, D8Mit359) in the female mice. Fine mapping with the entire F2 cohort and additional informative markers confirmed and narrowed the QTLs. The chromosome 8 QTL (EE8 F ) is homologous with two suggestive human QTLs and one significant rat QTL previously linked with exercise endurance. No effect of sex (P ϭ 0.33) or body weight (P ϭ 0.79) on exercise endurance was found in the F 2 cohort. These data indicate that genetic factors in distinct chromosomal regions may affect maximal exercise endurance in the inbred mouse. Whereas multiple genes are located in the identified QTL that could functionally affect exercise endurance, this study serves as a foundation for further investigations delineating the identity of genetic factors influencing maximum exercise endurance. candidate genes; aerobic capacity; genotyping SEVERAL RECENT STUDIES have shown that the maximal exercise endurance of an individual can impact all-cause mortality rates (31), mortality rates from hypertension (7), smoking-related and non-smoking-related cancers (21), and stroke (22). A tremendous amount of research has considered the modifying role of environmental factors on maximal aerobic exercise (e.g., training). It is well accepted that the variation seen in human maximal exercise endurance is due to the influence of genetic factors (3), and current estimations of the contribution of genetics to maximal exercise endurance range from Ϸ51% in humans (3) to 58 -90% in mice (23, 26) to 39% in rats (18).