Analysis Tools
homeostasis/metabolism
|
• under basal conditions, male homozygotes display reduced plasma corticosterone levels in the light phase relative to wild-type mice
• in contrast to ACTH, corticosterone levels are normally increased at the dark phase compared with those at the light phase, indicating that circadian variation in corticosterone secretion is unimpaired in mutant mice
• in response to i.p. administration of exogenous [Arg8]-vasopressin (AVP) at 0.5 g/kg, male homozygotes exhibit a significantly attenuated increase in circulating corticosterone levels, unlike wild-type male which show a dose-dependent increase in corticosterone secretion
• in response to stress, male homozygotes subjected to the forced swim test display significantly lower plasma corticosterone levels than wild-type males, although a similar rise in corticosterone above the basal level is observed
• however, male homozygotes show a normal corticotropin-releasing hormone (CRH)-induced corticosterone response relative to wild-type males
|
|
• under basal conditions, male homozygotes display reduced plasma ACTH levels in the light phase relative to wild-type mice
• unlike wild-type mice, male homozygotes fail to exhibit an increase in plasma ACTH levels at the third hour of the dark phase of the light cycle, indicating that circadian variation in ACTH secretion is blunted in mutant mice
• in response to i.p. administration of exogenous AVP (0.05 or 0.5 g/kg), male homozygotes fail to exhibit a significant increase in circulating ACTH levels, unlike wild-type male which show a dose-dependent increase in ACTH secretion
• in response to stress, male homozygotes subjected to the forced swim test show a significantly attenuated increase in plasma ACTH levels relative to wild-type males
• in vitro, AVP-induced ACTH release from mutant primary cultured pituitary cells is completely blunted
• in contrast, CRH-induced ACTH release from mutant primary cultured pituitary cells is comparable to that observed in wild-type pituitary cells
• also, male homozygotes show a normal CRH-induced ACTH response relative to wild-type males
|
endocrine/exocrine glands
|
• although adrenal gland histology is largely normal, the ratio of adrenal gland weight to body weight is significantly reduced in female, but no male, homozygotes relative to age-matched wild-type controls
• however, no significant weight differences are noted between female or male homozygotes and wild-type controls in brain, liver, kidney, and pituitary
• moreover, at 10 weeks of age, the cerebral cortex, hippocampus, amygdala, hypothalamus, and anterior pituitary appear morphological normal
|
