Failure to respond to endogenous or exogenous melatonin may cause nonphotoresponsiveness in Harlan Sprague Dawley rats

<p>Abstract</p> <p>Background</p> <p>Responsiveness to changing photoperiods from summer to winter seasons is an important but variable physiological trait in most temperate-zone mammals. Variation may be due to disorders of melatonin secretion or excretion, or to differences in physiological responses to similar patterns of melatonin secretion and excretion. One potential cause of nonphotoresponsiveness is a failure to secrete or metabolize melatonin in a pattern that reflects photoperiod length.</p> <p>Methods</p> <p>This study was performed to test whether a strongly photoresponsive rat strain (F344) and strongly nonphotoresponsive rat strain (HSD) have similar circadian urinary excretion profiles of the major metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), in long-day (L:D 16:8) and short-day (L:D 8:16) photoperiods. The question of whether young male HSD rats would have reproductive responses to constant dark or to supplemental melatonin injections was also tested. Urinary 24-hour aMT6s profiles were measured under L:D 8:16 and L:D 16:8 in young male laboratory rats of a strain known to be reproductively responsive to the short-day photoperiod (F344) and another known to be nonresponsive (HSD).</p> <p>Results</p> <p>Both strains exhibited nocturnal rises and diurnal falls in aMT6s excretion during both photoperiods, and the duration of the both strains' nocturnal rise was longer in short photoperiod treatments. In other experiments, young HSD rats failed to suppress reproduction or reduce body weight in response to either constant dark or twice-daily supplemental melatonin injections.</p> <p>Conclusion</p> <p>The results suggest that HSD rats may be nonphotoresponsive because their reproductive system and regulatory system for body mass are unresponsive to melatonin.</p

Data from: Body composition QTLs identified in intercross populations are reproducible in consomic mouse strains

Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL

Body Composition QTLs Identified in Intercross Populations Are Reproducible in Consomic Mouse Strains.

Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL

Data for Mouse Phenome Database_Reed_Bachmanov_June_2015

Contains body composition data for consomic mic

Adiposity QTL <i>Adip20</i> decomposes into at least four loci when dissected using congenic strains

<div><p>An average mouse in midlife weighs between 25 and 30 g, with about a gram of tissue in the largest adipose depot (gonadal), and the weight of this depot differs between inbred strains. Specifically, C57BL/6ByJ mice have heavier gonadal depots on average than do 129P3/J mice. To understand the genetic contributions to this trait, we mapped several quantitative trait loci (QTLs) for gonadal depot weight in an F₂ intercross population. Our goal here was to fine-map one of these QTLs, <i>Adip20</i> (formerly <i>Adip5</i>), on mouse chromosome 9. To that end, we analyzed the weight of the gonadal adipose depot from newly created congenic strains. Results from the sequential comparison method indicated at least four rather than one QTL; two of the QTLs were less than 0.5 Mb apart, with opposing directions of allelic effect. Different types of evidence (missense and regulatory genetic variation, human adiposity/body mass index orthologues, and differential gene expression) implicated numerous candidate genes from the four QTL regions. These results highlight the value of mouse congenic strains and the value of this sequential method to dissect challenging genetic architecture.</p></div

Gonadal adipose depot.

<p>Anatomical location of the gonadal adipose depot in a male mouse.</p

QTL confirmation from the consomic strains.

<p>Confirmation criterion–one or more sexes and one or more reciprocal strains differed in the expected direction using a p-value threshold adjusted for multiple testing (see <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141494#pone.0141494.t003" target="_blank">Table 3</a></b>). <i>Bdln4</i> and <i>Bdln5</i> are combined because they are both on chromosome 9.</p

QTLs detection in consomic mice: Average values of body size and composition measures in inbred and consomics strains.

<p>Body weight (top), body length (middle), and adiposity (bottom) in inbred and consomic strains (means ± SEM). Left panels: Strains with 129 genetic background. Right panels: Strains with B6 genetic background. Asterisks (*) indicate a nominal difference between consomic strain and its inbred host (p < .0.05), # indicates significant after correction for multiple testing (p<0.0056). ^~p = 0.0545. ^&borderline significance. ^§mice are heavier (top panel) but have similar gonadal weight, thus are leaner after adjustment for body weight.</p