title: Duper: a mutation that shortens hamster circadian period.
abstract: Three animals born to homozygous tau mutant (τ(ss), "super short") Syrian hamsters showed extremely short free-running periods of locomotor activity (τ(DD) of approximately 17.8 hours). Inbreeding produced 33 such "super duper" animals, which had a τ(DD) of 18.09 ± 0.05 hours, which was shorter than that of τ(ss) 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 τ(DD), we backcrossed super duper hamsters to unrelated τ(ss) animals. The F(1) pups uniformly had a τ(DD) similar to that of τ(ss) hamsters (19.89 ± 0.15 hours), but F(2) animals showed a 1:1 ratio of the 18- to 20-hour phenotypes. In contrast, the F(1) of a cross between super duper hamsters and τ(ss) animals presumed heterozygous for duper showed a 1:1 ratio of 18- to 20-hour phenotypes, and inbreeding of the super duper F(1) offspring uniformly produced F(2) pups with extremely short τ(DD) (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 F(2) pups that lack the mutant CK1ε allele, and these animals had a mean τ(DD) of 23.11 ± 0.04 hours. τ(DD) 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). τ(DD) shortened twice as much in τ(s) and τ(ss) hamsters than in wild-type animals that were homozygous for duper, indicating the presence of epistatic interactions. Assortment of phenotypes in the F(2) generation fit the expected distribution for expression of duper as recessive (χ(2) = 6.41, p > 0.1). Neither CK1ε nor CK1δ coding region base sequences differed between super duper and τ(ss) hamsters. The growth rate of super duper mutants is similar to that of τ(ss) animals but slightly but significantly reduced at particular postweaning time points. We conclude that duper represents a new mutation that substantially reduces τ(DD) and has significant effects on physiology and metabolism.
authors.affiliation: Department of Biology and Program in Neuroscience and Behavior, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Monecke
authors.forename: Judy McKinley
authors.initials: JM
authors.lastname: Brewer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Krug
authors.forename: Eric L
authors.initials: EL
authors.lastname: Bittman
mesh_terms: D000818:Animals; D001483:Base Sequence; D048149:Casein Kinase 1 epsilon / Q000235:genetics; D048148:Casein Kinase Idelta / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D006224:Cricetinae; D003433:Crosses, Genetic; D017931:DNA Primers; D006579:Heterozygote; D008647:Mesocricetus; D009154:Mutation; D016875:tau Proteins / Q000235:genetics
chemical_list: D017931:DNA Primers; D016875:tau Proteins; D048149:Casein Kinase 1 epsilon; D048148:Casein Kinase Idelta