Duper

Abstract

Three animals born to homozygous tau mutant (τss, “super short”) Syrian hamsters showed extremely short free-running periods of locomotor activity (τDD of approximately 17.8 hours). Inbreeding produced 33 such “super duper” animals, which had a τDD of 18.09 ± 0.05 hours, which was shorter than that of τss hamsters (20.66 ± 0.07 hours, p < 0.001). To test the hypothesis that a gene ( Duper) is responsible for a 2-hour shortening of τDD, we backcrossed super duper hamsters to unrelated τss animals. The F1 pups uniformly had a τDD similar to that of τss hamsters (19.89 ± 0.15 hours), but F2 animals showed a 1:1 ratio of the 18- to 20-hour phenotypes. In contrast, the F1 of a cross between super duper hamsters and τss animals presumed heterozygous for duper showed a 1:1 ratio of 18- to 20-hour phenotypes, and inbreeding of the super duper F1 offspring uniformly produced F2 pups with extremely short τDD (17.86 ± 0.5 hours). We isolated the duper mutation on a wild-type background through crossing of super duper with wild-type animals. Restriction digests identified short-period F2 pups that lack the mutant CK1ε allele, and these animals had a mean τDD of 23.11 ± 0.04 hours. τDD of duper hamsters born and raised in DD was significantly shorter than in hamsters raised in 14L:10D (21.92 ± 0.12 hours, p < 0.0001). τDD shortened twice as much in τs and τss hamsters than in wild-type animals that were homozygous for duper, indicating the presence of epistatic interactions. Assortment of phenotypes in the F2 generation fit the expected distribution for expression of duper as recessive (χ2 = 6.41, p > 0.1). Neither CK1ε nor CK1δ coding region base sequences differed between super duper and τss hamsters. The growth rate of super duper mutants is similar to that of τss animals but slightly but significantly reduced at particular postweaning time points. We conclude that duper represents a new mutation that substantially reduces τDD and has significant effects on physiology and metabolism.