Loss of magel2, a candidate gene for features of Prader-Willi syndrome, impairs reproductive function in mice

• Published in: PloS one Vol. 4; no. 1; p. e4291
• Main Authors: Mercer, Rebecca E, Wevrick, Rachel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.01.2009; Public Library of Science (PLoS)
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Age; Alleles; Animals; Antigens, Neoplasm - metabolism; Behavior; Breeding; Circadian rhythm; Circadian rhythms; Estrous Cycle - genetics; Estrus; Female; Females; Fertility; Gene Expression Regulation; Genes; Genetic aspects; Genetics and Genomics/Complex Traits; Genetics and Genomics/Disease Models; Genetics and Genomics/Medical Genetics; Hormones; Infertility; Male; Males; Metabolism; Mice; Models, Genetic; Mutation; Nervous system; Odors; Physiological aspects; Prader-Willi syndrome; Prader-Willi Syndrome - genetics; Pregnancy; Proteins - metabolism; Puberty; Reproduction - genetics; Rhythm; Rodents; Smell; Sperm; Testosterone; Testosterone - metabolism; Weaning; Weight reduction
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004291

MAGEL2 is one of several genes typically inactivated in the developmental obesity disorder Prader-Willi syndrome (PWS). The physiological consequences of loss of MAGEL2, but without the concurrent loss of other PWS genes, are not well understood. Gene-targeted mutation of Magel2 in mice disrupts circadian rhythm and metabolism causing reduced total activity, reduced weight gain before weaning, and increased adiposity after weaning. We now show that loss of Magel2 in mice causes reduced fertility in both males and females through extended breeding intervals and early reproductive decline and termination. Female Magel2-null mice display extended and irregular estrous cycles, while males show decreased testosterone levels, and reduced olfactory preference for female odors. Our results suggest that loss of MAGEL2 contributes to the reproductive deficits seen in people with PWS, and further highlights the role of normal circadian rhythm in the maintenance of fertility.