Analysis Tools
mortality/aging
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• approximately 28% of homozygous mutant mice died after weaning
• survivors were viable, fertile, and displayed no obvious phenotype
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behavior/neurological
| N |
• homozygous mutant mice displayed no differences relative to wild-type mice in various learning tasks (M. Sauvage, T. Steckler, unpublished)
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• homozygous mutant mice and wild-type mice displayed a similar water consumption and initial alcohol intake preference under stress-free housing conditions
• homozygous mutant and wild-type mice displayed normal alcohol metabolism in terms of blood alcohol concentration, indicating normal acute clearance of ethanol
• notably, 3 weeks after repeated social defeat stress, homozygous mutant mice (129/Ola x CD1 F2) offered water and ethanol (8% v/v) in a two-bottle free-choice paradigm displayed a significant increase in voluntary alcohol intake, whereas wild-type mice displayed no change in alcohol intake; during the post-stress phase, homozygous mutant mice consumed considerably larger amounts of alcohol than wild-type mice
• also, homozygous mutant mice exposed to forced swimming during a second period of repeated stress, progressively increased their alcohol intake after about 3 weeks; this post-stress alcohol intake was significantly higher in mutant mice relative to wild-type mice, and persisted at an elevated level throughout their life
• enhanced and delayed stress-induced alcohol consumption in 129/Ola x CD1 F2 homozygous mutants was associated with increased protein levels of the GRIN2B subunit in the hippocampus, amygdala, and nucleus accumbens; this subunit is an ethanol-sensitive site and is also influenced by stress
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• following ethanol withdrawal, all groups of mice displayed reduced exploratory activity in an open field
• homozygous mutant mice differed from wild-type and heterozygous mice under ethanol withdrawal but not under basal conditions in the number of animals avoiding the lit compartment in the light-dark box: wild-type animals were more affected by alcohol withdrawal than mutants
• during ethanol withdrawal, homozygous mutant mice exhibited lower latencies to enter the lit compartment than wild-type mice, made no entries and spent more time within the lit compartment than wild-type animals
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• under basal conditions, homozygous mutant mice were more active than heterozygous mutants or wild-type mice: homozygotes displayed increased exploratory activity in an open field, indicating reduced anxiety-like performance
• under basal conditions, homozygous mutant mice displayed significantly lower latencies to enter the lit compartment, showed a higher percentage of entries into the lit compartment and spent more time there than wild-type mice
• following ethanol withdrawal, all groups of mice displayed reduced exploratory activity in an open field
• homozygous mutant mice differed from wild-type and heterozygous mice under ethanol withdrawal but not under basal conditions in the number of animals avoiding the lit compartment in the light-dark box: wild-type animals were more affected by alcohol withdrawal than mutants
• during ethanol withdrawal, homozygous mutant mice exhibited lower latencies to enter the lit compartment than wild-type mice, made no entries and spent more time within the lit compartment than wild-type animals
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endocrine/exocrine glands
| N |
• histology and in situ hybridization analysis of the pituitary gland revealed no anatomic abnormalities, and no differences in either cell densities in the entire pituitary gland, or in the cell densities of corticotrophs and melanotrophs
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• histology of the cortex of the adrenal gland (including the zona fasciculata) of wild-type and mutant mice did not reveal any obvious morphological differences; however, the diameter of the mutant adrenal medulla was significantly reduced (49%)
• the densities of chromaffin cells remained unaltered
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homeostasis/metabolism
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• homozygous mutant males and females displayed normal basal levels of POMC1 (ACTH)
• female homozygous mutant mice had significantly reduced (~3-fold) basal levels of plasma corticosterone relative to wild-type female mice; male homozygous mutant mice had undetectable levels of plasma corticosterone
• homozygous mutant mice showed an impaired HPA axis response to forced-swim stress: compared with wild-type, homozygous females and males failed to significantly increase circulating levels of POMC1 (ACTH); also, stress-induced plasma corticosterone levels were significantly higher (7-fold) in wild-type than in homozygous females and males
• immunohistochemical analysis indicated accumulation of CRH (corticotropin releasing hormone) neuropeptide in the paraventricular nucleus of the hypothalamus, the amygdala, the hippocampus, and the cerebral complex in homozygous mutants
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nervous system
| N |
• in homozygous mutant mice, the cerebral cortex, hippocampus, amygdala, and hypothalamus appeared morphologically normal
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