title: Steroid deficiency syndromes in mice with targeted disruption of Cyp11a1.
abstract: Steroid deficiencies are diseases affecting salt levels, sugar levels, and sexual differentiation. To study steroid deficiency in more detail, we used a gene-targeting technique to insert a neo gene into the first exon to disrupt Cyp11a1, the first gene in steroid biosynthetic pathways. Cyp11a1 null mice do not synthesize steroids. They die shortly after birth, but can be rescued by steroid injection. Due to the lack of feedback inhibition by glucocorticoid, their circulating ACTH levels are exceedingly high; this results in ectopic Cyp21 gene expression in the testis. Male Cyp11a1 null mice are feminized with female external genitalia and underdeveloped male accessory sex organs. Their testis, epididymis, and vas deferens are present, but undersized. In addition, their adrenals and gonads accumulate excessive amounts of lipid. The lack of steroid production, abnormal gene expression, and aberrant reproductive organ development resemble various steroid deficiency syndromes, making these mice good models for studies of steroid function and regulation.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors.forename: Meng-Chun
authors.initials: MC
authors.lastname: Hu
authors.forename: Nai-Chi
authors.initials: NC
authors.lastname: Hsu
authors.forename: Noomen Ben
authors.initials: NB
authors.lastname: El Hadj
authors.forename: Chin-I
authors.initials: CI
authors.lastname: Pai
authors.forename: Hsueh-Ping
authors.initials: HP
authors.lastname: Chu
authors.forename: Chi-Kuang Leo
authors.initials: CK
authors.lastname: Wang
authors.forename: Bon-Chu
authors.initials: BC
authors.lastname: Chung
mesh_terms: D000311:Adrenal Glands / Q000002:abnormalities; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000172:deficiency* / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004573:Electrolytes / Q000378:metabolism; D005262:Feminization / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018390:Gene Targeting; D005837:Genitalia, Male / Q000002:abnormalities; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013255:Steroid 21-Hydroxylase; D013256:Steroids / Q000096:biosynthesis*; D013577:Syndrome
chemical_list: D004573:Electrolytes; D013256:Steroids; D003577:Cytochrome P-450 Enzyme System; D013255:Steroid 21-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme