Table 1.

Phenotypic characteristics of transgenic modifications in genes for components of the CRF family of peptide hormones and receptors.

Genotype	Transgenic Modification	Gross Phenotype and Biological Characteristics
Crh -/-	Knockout [5]	Progeny from homozygous Crh-/- die within 12 h after birth due to lung hyperplasia. Can be rescued after intervention with exogenous glucocorticoids. Marked fetal glucocorticoid deficiency, but normal postnatal growth, fertile.
Crh-OE or Crh-Tg	Constitutive overexpression [46]	Elevated basal plasma corticosterone, normal basal ACTH, and HPA axis responses to stress.
Crh-OE or Crh-Tg	Overexpression [49]	Cushing’s syndrome-like symptoms. Increased hypothalamic CRF expression, increased circulating corticosterone and adrenocorticotrophic hormone (ACTH). Delayed and attenuated HPA axis responses to stress.
Ucn1 -/-	Knockout [53,54]	Significant auditory deficit and acoustic startle responses in both lines. Increased anxiety-like responses in one line, but not the other. No overt phenotypic abnormality. Fertile.
Ucn2 -/-	Knockout [55,56]	Metabolic phenotype suggesting role in glucose homeostasis. No other overt phenotypic abnormality. Fertile. Female, but not male knockout show increased basal ACTH, corticosterone rhythm, decreased fluid intake, and depression-like behavior.
Ucn3 -/-	Knockout [57]	Regulation of glucose homeostasis. No change in anxiety- or depression-like behaviors. No other gross phenotype. Fertile.
Ucn1-/-/Ucn2-/-	Double knockout [58]	Impaired recovery responses to stress. Fertile.
Ucn1-/-/Ucn2-/-/Ucn3-/-	Triple knockout [6]	Reveal urocortins’ role in stress recovery; increased anxiety-like behavior in response to stress. May have impaired cardiac and reproductive functions.
Crhr1 -/-	Knockout [59]	Low plasma corticosterone, impaired HPA axis responses, decreased anxiety-like responses. Progeny from heterozygous mice are fertile and without overt phenotype, but male progeny show 15% mortality. Progeny from homozygous female dam die 2 days after birth. Adrenal gland atrophy.
Crhr2 -/-	Knockout [60,61]	Hypertensive, increased anxiety-like behavior, hypersensitive to HPA axis stress responsive, fertile, no other overt phenotype.
Crhr1-/-/Crhr2 -/-	Double knockout [62]	Sexually dimorphic stress responses: female mice have reduced anxiety-like behavior, whereas male mice show increased anxiety-like behavior.