title: The glucocorticoid-induced leucine zipper (gilz/Tsc22d3-2) gene locus plays a crucial role in male fertility.
abstract: The glucocorticoid-induced leucine zipper (Tsc22d3-2) is a widely expressed dexamethasone-induced transcript that has been proposed to be important in immunity, adipogenesis, and renal sodium handling based on in vitro studies. To address its function in vivo, we have used Cre/loxP technology to generate mice deficient for Tsc22d3-2. Male knockout mice were viable but surprisingly did not show any major deficiencies in immunological processes or inflammatory responses. Tsc22d3-2 knockout mice adapted to a sodium-deprived diet and to water deprivation conditions but developed a subtle deficiency in renal sodium and water handling. Moreover, the affected animals developed a mild metabolic phenotype evident by a reduction in weight from 6 months of age, mild hyperinsulinemia, and resistance to a high-fat diet. Tsc22d3-2-deficient males were infertile and exhibited severe testis dysplasia from postnatal d 10 onward with increases in apoptotic cells within seminiferous tubules, an increased number of Leydig cells, and significantly elevated FSH and testosterone levels. Thus, our analysis of the Tsc22d3-2-deficient mice demonstrated a previously uncharacterized function of glucocorticoid-induced leucine zipper protein in testis development.
authors.affiliation: Departments of Pharmacology and Toxicology, University of Lausanne, CH-1005 Lausanne, Switzerland.
authors.forename: Philippe Emmanuel
authors.initials: PE
authors.lastname: Suarez
authors.forename: Elena Gonzalez
authors.initials: EG
authors.lastname: Rodriguez
authors.forename: Rama
authors.initials: R
authors.lastname: Soundararajan
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mérillat
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Stehle
authors.forename: Samuel
authors.initials: S
authors.lastname: Rotman
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Voirol
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Olaf
authors.initials: O
authors.lastname: Gross
authors.forename: Virginie
authors.initials: V
authors.lastname: Pétrilli
authors.forename: Karim
authors.initials: K
authors.lastname: Nadra
authors.forename: Anne
authors.initials: A
authors.lastname: Wilson
authors.forename: Friedrich
authors.initials: F
authors.lastname: Beermann
authors.forename: François Pierre
authors.initials: FP
authors.lastname: Pralong
authors.forename: Marc
authors.initials: M
authors.lastname: Maillard
authors.forename: David
authors.initials: D
authors.lastname: Pearce
authors.forename: Roman
authors.initials: R
authors.lastname: Chrast
authors.forename: Bernard Claude
authors.initials: BC
authors.lastname: Rossier
authors.forename: Edith
authors.initials: E
authors.lastname: Hummler
mesh_terms: D050156:Adipogenesis; D000818:Animals; D001835:Body Weight; D002452:Cell Count; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D056426:Genetic Loci; D006946:Hyperinsulinism / Q000235:genetics; D007107:Immune System / Q000254:growth & development; D007155:Immunologic Factors / Q000494:pharmacology; D007248:Infertility, Male / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics; D013154:Spleen / Q000473:pathology; D013737:Testis / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*
chemical_list: D016207:Cytokines; C498608:Dsip1 protein, mouse; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D020033:Protein Isoforms; D014157:Transcription Factors; D003907:Dexamethasone