Analysis Tools
mortality/aging
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• 15% of homozygous mutant male mice born from mating of heterozygotes died between 3 and 12 weeks of age; no death was observed in female mutant mice or in control mice
• notably, almost all of the progeny born to homozygous mutant females died within 48 hours after birth due to neonatal respiratory distress
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behavior/neurological
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• during the retrieval trial of a two-trial spatial memory task, wild-type controls made more visits to the novel arm and visited it longer than the two familiar arms of a Y-maze apparatus; in contrast, homozygous mutant males failed to display any increase in the level of exploration of the novel arm, indicating a deficit in spatial recognition memory
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• following food deprivation, acute third ventricular injection of urocortin reduced initial (0-1.5 hr) food intake in wild-type mice, but not mutant mice; thereafter, urocortin effects on food intake were genotype-independent
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• male mutant mice displayed significantly reduced anxiety-like behavior on the elevated plus maze (EPM) and in the light/dark emergence task
(J:48280)
• male mutant mice showed no differences in general locomotor activity or in closed arm activity in the EPM model
(J:48280)
• corticosterone administration did not affect the performance of either control or homozygous mutant males in the EPM model
(J:48280)
• compared with wild-type mice, homozygous mutant male mice displayed increased exploratory behavior in both the EPM and the Black and White test box models, indicating reduced anxiety-like performance
(J:56443)
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endocrine/exocrine glands
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• no gross anatomical abnormalities were observed in all three lobes of the pituitary glands, and corticotrope development appeared normal
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• histologic analysis revealed hypoplasia of the zona fasciculata (corticosterone-producing region) of the adrenal cortex
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• homozygous mutant mice displayed atrophy of the adrenal gland due to agenesis of the adrenal cortex
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• histologic analysis revealed hypoplasia of the zona fasciculata (corticosterone-producing region) of the adrenal cortex; other regions of the adrenal glands appeared normal
• postnatal treatment with POMC1 (ACTH) starting at P10 through P21 rescued the adrenal atrophy phenotype
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homeostasis/metabolism
| N |
• homozygous mutants displayed normal food and fluid intake during ad libitum and post-deprivation conditions; restoration of the glucocorticoid circadian rhythm through addition of corticosterone in drinking water had little effects on these parameters
• a 7-day third ventricular infusion of urocortin transiently reduced ad libitum food intake in wild-type and corticosterone-replaced homozygous mutant mice to a similar extent; body weight reduction during urocotrin infusion paralleled food intake in wild-type mice, but persisted throughout the infusion in mutant mice
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• homozygous mutant mice displayed normal basal levels of POMC1 (ACTH)
• both male and female homozygous mutant mice displayed significantly low plasma levels of corticosterone relative to control mice; the typical diurnal rise in circulating corticosterone that normally occurs in the afternoon was absent
• homozygous mutant mice displayed an impaired HPA axis response to physical-restraint stress: mutants failed to significantly increase circulating levels of POMC1 (ACTH) and corticosterone; in addition, the amplitude of corticosterone response to stress was severely blunted
• immunohistochemistry revealed a significant increase in CRH expression in the mutant paraventricular nuclei of the hypothalamus, indicating a reduced negative feedback response due to lowered corticosterone levels
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respiratory system
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• at P1
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• at P1, offspring born to female homozygous mutants displayed severe lung dysplasia
• in utero treatment of mutant females with corticosterone in drinking water from E12 through P14, corrected the lung dysplasia phenotype and resulted in a normal postnatal survival rate of progeny born to homozygous mutant females
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• at P1, offspring born to female homozygous mutants displayed alveolar collapse and reactive emphysema with intra-alveolar hemorrhage and hemosiderotic deposition; hyaline membranes were absent
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• neonatal mortality noted in the progeny of homozygous mutant mice was attributed to respiratory distress
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cardiovascular system
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• at P1
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