Myg1-deficient mice display alterations in stress-induced responses and reduction of sex-dependent behavioural differences.
Myg1 (Melanocyte proliferating gene 1) is a highly conserved and ubiquitously expressed gene, which encodes a protein with mitochondrial and nuclear localization. In the current study we demonstrate a gradual decline of Myg1 expression during the postnatal development of the mouse brain that suggests relevance for Myg1 in developmental processes. To study the effects of Myg1 loss-of-function, we created Myg1-deficient (-/-) mice by displacing the entire coding sequence of the gene. Initial phenotyping, covering a multitude of behavioural, cognitive, neurological, physiological and stress-related responses, revealed that homozygous Myg1 (-/-) mice are vital, fertile and display no gross abnormalities. Myg1 (-/-) mice showed an inconsistent pattern of altered anxiety-like behaviour in different tests. The plus-maze and social interaction tests revealed that male Myg1 (-/-) mice were significantly less anxious than their wild-type littermates; female (-/-) mice showed increased anxiety in the locomotor activity arena. Restraint-stress significantly reduced the expression of the Myg1 gene in the prefrontal cortex of female wild-type mice and restrained female (-/-) mice showed a blunted corticosterone response, suggesting involvement of Myg1 in stress-induced responses. The main finding of the present study was that Myg1 invalidation decreases several behavioural differences between male and female animals that were obvious in wild-type mice, indicating that Myg1 contributes to the expression of sex-dependent behavioural differences in mice. Taken together, we provide evidence for the involvement of Myg1 in anxiety- and stress-related responses and suggest that Myg1 contributes to the expression of sex-dependent behavioural differences.
Philips
Mari-Anne
MA
Department of Physiology, University of Tartu, 19 Ravila Street, Tartu, Estonia. maphilips@gmail.com
Abramov
Urho
U
Lilleväli
Kersti
K
Luuk
Hendrik
H
Kurrikoff
Kaido
K
Raud
Sirli
S
Plaas
Mario
M
Innos
Jürgen
J
Puussaar
Triinu
T
Kõks
Sulev
S
Vasar
Eero
E
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D003345:Corticosterone / Q000097:blood*; D004734:Energy Metabolism / Q000235:genetics; D005106:Exploratory Behavior / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D005838:Genotype; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017288:Pain Threshold / Q000502:physiology; D045442:Rotarod Performance Test; D012727:Sex Characteristics; D012737:Sex Factors; D012919:Social Behavior; D013037:Spatial Behavior / Q000502:physiology; D015431:Weight Loss / Q000187:drug effects
D008070:Lipopolysaccharides; C541353:MYG1 protein, mouse; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D003345:Corticosterone