An N-ethyl-N-nitrosourea induced corticotropin-releasing hormone promoter mutation provides a mouse model for endogenous glucocorticoid excess.

[cushing syndrome]

Cushing 's syndrome , which is characterized by excessive circulating glucocorticoid concentrations , may be due to ACTH-dependent or -independent causes that include anterior pituitary and adrenal cortical tumors , respectively . ACTH secretion is stimulated by CRH , and we report a mouse model for Cushing 's syndrome due to an N-ethyl-N-nitrosourea (ENU ) induced Crh mutation at -120 bp of the promoter region , which significantly increased luciferase reporter activity and was thus a gain-of-function mutation . Crh (-120 /+) mice , when compared with wild-type littermates , had obesity , muscle wasting , thin skin , hair loss , and elevated plasma and urinary concentrations of corticosterone . In addition , Crh (-120 /+) mice had hyperglycemia , hyperfructosaminemia , hyperinsulinemia , hypercholesterolemia , hypertriglyceridemia , and hyperleptinemia but normal adiponectin . Crh (-120 /+) mice also had low bone mineral density , hypercalcemia , hypercalciuria , and decreased concentrations of plasma PTH and osteocalcin . Bone histomorphometry revealed Crh (-120 /+) mice to have significant reductions in mineralizing surface area , mineral apposition , bone formation rates , osteoblast number , and the percentage of corticoendosteal bone covered by osteoblasts , which was accompanied by an increase in adipocytes in the bone marrow . Thus , a mouse model for Cushing 's syndrome has been established , and this will help in further elucidating the pathophysiological effects of glucocorticoid excess and in evaluating treatments for corticosteroid-induced osteoporosis .

Diseases
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Diseases presenting "respectively" symptom

adrenal incidentaloma

allergic bronchopulmonary aspergillosis

alpha-thalassemia

benign recurrent intrahepatic cholestasis

carcinoma of the gallbladder

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cushing syndrome

cystinuria

dedifferentiated liposarcoma

dentin dysplasia

dentinogenesis imperfecta

epidermolysis bullosa simplex

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

harlequin ichthyosis

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

holt-oram syndrome

kallmann syndrome

lamellar ichthyosis

liposarcoma

neonatal adrenoleukodystrophy

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyruvate dehydrogenase deficiency

scrub typhus

triple a syndrome

von hippel-lindau disease

well-differentiated liposarcoma

wolf-hirschhorn syndrome

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