RRC ID 5992
Author Kasahara T, Abe K, Mekada K, Yoshiki A, Kato T.
Title Genetic variation of melatonin productivity in laboratory mice under domestication.
Journal Proc. Natl. Acad. Sci. U.S.A.
Abstract Melatonin is a pineal hormone produced at night; however, many strains of laboratory mice are deficient in melatonin. Strangely enough, the gene encoding HIOMT enzyme (also known as ASMT) that catalyzes the last step of melatonin synthesis is still unidentified in the house mouse (Mus musculus) despite the completion of the genome sequence. Here we report the identification of the mouse Hiomt gene, which was mapped to the pseudoautosomal region (PAR) of sex chromosomes. The gene was highly polymorphic, and nonsynonymous SNPs were found in melatonin-deficient strains. In C57BL/6 strain, there are two mutations, both of which markedly reduce protein expression. Mutability of the Hiomt likely due to a high recombination rate in the PAR could be the genomic basis for the high prevalence of melatonin deficiency. To understand the physiologic basis, we examined a wild-derived strain, MSM/Ms, which produced melatonin more under a short-day condition than a long-day condition, accompanied by increased Hiomt expression. We generated F2 intercrosses between MSM/Ms and C57BL/6 strains and N2 backcrosses to investigate the role of melatonin productivity on the physiology of mice. Although there was no apparent effect of melatonin productivity on the circadian behaviors, testis development was significantly promoted in melatonin-deficient mice. Exogenous melatonin also had the antigonadal action in mice of a melatonin-deficient strain. These findings suggest a favorable impact of melatonin deficiency due to Hiomt mutations on domestic mice in breeding colonies.
Volume 107(14)
Pages 6412-7
Published 2010-4-6
DOI 10.1073/pnas.0914399107
PII 0914399107
PMID 20308563
PMC PMC2851971
MeSH Acetylserotonin O-Methyltransferase / genetics* Animals Behavior, Animal Cell Line Circadian Rhythm DNA, Complementary / genetics Female Genetic Variation* Humans Male Melatonin / biosynthesis* Mice Mice, Inbred Strains / genetics* Molecular Sequence Data Ovary / growth & development Ovary / metabolism Phylogeny Testis / growth & development Testis / metabolism
IF 9.504
Times Cited 48
DNA material MSM Mouse BAC (RDB04214) MSMg01-318O12
Mice BFM/2Ms