behavior/neurological
• double homozygous mutant mice showed a sexually dichotomous anxiety-like behavior on the elevated plus maze: female double mutant mice displayed anxiolytic-like behavior, whereas male double mutant mice showed significantly increased anxiety-like behavior relative to females
• no significant differences were observed in center visits between female and male double mutant mice in the open-field test; however, female double mutant mice produced significantly fewer fecal boli, suggesting an anxiolytic-like behavior
• notably, the dam's genotype affects the anxiety-like behavior of double mutant males: a pup born to a heterozygous or homozygous mutant dam exhibits significantly increased anxiety-like behavior, regardless of that pup's genotype
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endocrine/exocrine glands
N |
• histology of the pituitary gland showed no anatomic abnormalities
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• histologic analysis revealed hypoplasia of the zona fasciculata (corticosterone-producing region) of the adrenal cortex
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• similar to Crhr1tm1Klee mutant mice, double mutant mice displayed atrophy of the adrenal gland due to agenesis of the adrenal cortex (hypoplasia of the zona fasciculata region)
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homeostasis/metabolism
• double homozygous mutant mice showed significantly lower basal levels of corticosterone compared to Crhr1tm1Klee single mutant mice; in contrast, basal levels of POMC1 (ACTH) did not differ between control, Crhr1tm1Klee single-, Crhr2tm1Klee single-, and double mutant mice
• double homozygous mutant mice displayed a minimal HPA axis response to physical-restraint stress, with significantly lower POMC1 (ACTH) and corticosterone levels compared to Crhr1tm1Klee single mutant mice
• CRH mRNA levels were increased in Crhr1tm1Klee single- and double-mutant mice, and urocortin-3 and arginine vasopressin mRNA levels were increased in Crhr2tm1Klee single- and double-mutant mice
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