title: Deletion of selenoprotein M leads to obesity without cognitive deficits.
abstract: Selenium is an essential trace element that is co-translationally incorporated into selenoproteins in the form of the 21st amino acid, selenocysteine. This class of proteins largely functions in oxidation-reduction reactions and is critically involved in maintaining proper redox balance essential to health. Selenoprotein M (SelM) is a thioredoxin-like endoplasmic reticulum-resident protein that is highly expressed in the brain and possesses neuroprotective properties. In this study, we first assessed the regional pattern of SelM expression in the mouse brain to provide insights into the potential functional implications of this protein in physiology and behavior. Next, we generated transgenic mice with a targeted deletion of the SelM gene and subjected them to a battery of neurobehavioral tests to evaluate motor coordination, locomotion, and cognitive function in comparison with wild-type controls. Finally, these mice were tested for several measures of metabolic function and body composition. Our results show that SelM knock-out (KO) mice display no deficits in measures of motor coordination and cognitive function but exhibit increased weight gain, elevated white adipose tissue deposition, and diminished hypothalamic leptin sensitivity. These findings suggest that SelM plays an important role in the regulation of body weight and energy metabolism.
authors.affiliation: From the Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96813. Electronic address: mwpitts@hawaii.edu.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Pitts
authors.affiliation: From the Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96813.
authors.forename: Mariclair A
authors.initials: MA
authors.lastname: Reeves
authors.affiliation: From the Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96813.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Hashimoto
authors.affiliation: From the Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96813.
authors.forename: Ashley
authors.initials: A
authors.lastname: Ogawa
authors.affiliation: From the Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96813.
authors.forename: Penny
authors.initials: P
authors.lastname: Kremer
authors.affiliation: From the Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96813.
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Seale
authors.affiliation: From the Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96813.
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Berry
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000235:genetics; D003071:Cognition; D004734:Energy Metabolism; D017353:Gene Deletion; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008124:Locomotion / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020738:Leptin; D009419:Nerve Tissue Proteins; D051140:Selenoproteins; C499178:Sepm protein, mouse
keywords: Energy Metabolism; Hypothalamus; Obesity; Oxidative Stress; Selenoprotein