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Genetic variation of melatonin productivity in laboratory mice under domestication.

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.

SUBMITTER: Kasahara T

PROVIDER: S-EPMC2851971 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Genetic variation of melatonin productivity in laboratory mice under domestication.

Kasahara Takaoki T Abe Kuniya K Mekada Kazuyuki K Yoshiki Atsushi A Kato Tadafumi T

Proceedings of the National Academy of Sciences of the United States of America 20100322 14

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 polym ...[more]

PMID: 20308563

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Project description:BACKGROUND: The transcript levels of many genes exhibit significant variation in tissue samples from inbred laboratory mice. A microarray experiment was designed to separate transcript abundance variation across samples from adipose, heart, kidney, and liver tissues of C57BL/6J mice into within-mouse and between-mouse components. Within-mouse variance captures variation due to heterogeneity of gene expression within tissues, RNA-extraction, and array processing. Between-mouse variance reflects differences in transcript levels between these genetically identical mice. Many biological sources can contribute to heterogeneous transcript levels within a tissue sample including inherent stochasticity of biochemical processes such as intrinsic and extrinsic noise within cells and differences in cell-type composition which can result from heterogeneity of stem and progenitor cell populations. Differences in global signaling patterns between individuals and micro-environmental influences such as interactions with pathogens and cage mates can also contribute to variation, but are likely to contribute more to the between-mouse variance component. RESULTS: The nature and extent of transcript abundance variation differs across tissues. Adipose has the largest total variance and the largest within-mouse variance. Liver has the smallest total variance, but it has the most between-mouse variation. Genes with high variability can be classified into groups with correlated patterns of expression that are enriched for specific biological functions. Variation between mice is associated with circadian rhythm, growth hormone signaling, immune response, androgen regulation, lipid metabolism, and the extracellular matrix. Genes showing correlated patterns of within mouse variation were also associated with biological functions, spatial connectivity of stochastic variation and heterogeneity of cell types within tissues. CONCLUSIONS: Genetically identical mice are individuals and they can experience different outcomes for medically important traits. This is reflected in the stochastic variation in gene expression observed between genetically identical mice. Much of the stochasticity has organismal, tissue, or spatial connectivity. Prior knowledge of the genes and functional classes of genes that are likely to vary in the absence of experimental perturbations, whether these are genetic or environmental, can inform experimental design decisions and the interpretation of gene expression data. Variation in gene expression in genetically identical mice sheds light on the impact of stochastic and micro-environmental factors and their phenotypic consequences.

Dataset Information

Genetic variation of melatonin productivity in laboratory mice under domestication.

Publications

Genetic variation of melatonin productivity in laboratory mice under domestication.

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