The Glucocorticoid-Induced Leucine Zipper (Gilz/Tsc22d3-2) Gene Locus Plays a Crucial Role in Male Fertility

Author:

Suarez Philippe Emmanuel1,Rodriguez Elena Gonzalez1,Soundararajan Rama2,Mérillat Anne-Marie1,Stehle Jean-Christophe3,Rotman Samuel3,Roger Thierry4,Voirol Marie-Jeanne5,Wang Jian2,Gross Olaf6,Pétrilli Virginie6,Nadra Karim7,Wilson Anne8,Beermann Friedrich9,Pralong François Pierre5,Maillard Marc10,Pearce David2,Chrast Roman7,Rossier Bernard Claude1,Hummler Edith1

Affiliation:

1. Departments of Pharmacology and Toxicology (P.E.S., E.G.R., A.-M.M., B.C.R., E.H.), University of Lausanne, CH-1005 Lausanne, Switzerland;

2. Division of Nephrology (R.S., J.W., D.P.), Department of Medicine, University of California, San Francisco, California 94122;

3. Institute of Pathology (J.-C.S., S.R.) CHUV and University of Lausanne, CH-1011 Lausanne, Switzerland;

4. Service of Infectious Diseases (T.R.), Department of Medicine; and Service of Endocrinology, Diabetology, CHUV and University of Lausanne, CH-1011 Lausanne, Switzerland;

5. Metabolism (M.-J.V., F.P.P.), Department of Medicine, CHUV and University of Lausanne, CH-1011 Lausanne, Switzerland;

6. Department of Biochemistry (O.G., V.P.), University of Lausanne, CH-1066 Epalinges, Switzerland;

7. Medical Genetics (K.N., R.C.), University of Lausanne, CH-1005 Lausanne, Switzerland;

8. Ludwig Center for Cancer Research of the University of Lausanne (A.W.), University of Lausanne, CH-1066 Epalinges, Switzerland;

9. Swiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Fédérale de Lausanne (F.B.), CH-1015 Lausanne, Switzerland

10. Service of Nephrology (M.M.), Centre Hospitalier Universitaire Vaudois (CHUV);, CHUV and University of Lausanne, CH-1011 Lausanne, Switzerland;

Abstract

AbstractThe 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.

Publisher

The Endocrine Society

Subject

Endocrinology,Molecular Biology,General Medicine

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