TY - JOUR
T1 - The glucocorticoid-induced leucine zipper (Gilz/Tsc22d3-2) gene locus plays a crucial role in male fertility
AU - Suarez, Philippe Emmanuel
AU - Rodriguez, Elena Gonzalez
AU - Soundararajan, Rama
AU - Mérillat, Anne Marie
AU - Stehle, Jean Christophe
AU - Rotman, Samuel
AU - Roger, Thierry
AU - Voirol, Marie Jeanne
AU - Wang, Jian
AU - Gross, Olaf
AU - Pétrilli, Virginie
AU - Nadra, Karim
AU - Wilson, Anne
AU - Beermann, Friedrich
AU - Pralong, François Pierre
AU - Maillard, Marc
AU - Pearce, David
AU - Chrast, Roman
AU - Rossier, Bernard Claude
AU - Hummler, Edith
PY - 2012/6
Y1 - 2012/6
N2 - The glucocorticoid-induced leucine zipper (Tsc22d3-2) is a widely expressed dexamethasoneinduced 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.
AB - The glucocorticoid-induced leucine zipper (Tsc22d3-2) is a widely expressed dexamethasoneinduced 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.
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U2 - 10.1210/me.2011-1249
DO - 10.1210/me.2011-1249
M3 - Article
C2 - 22556341
AN - SCOPUS:84861211156
SN - 0888-8809
VL - 26
SP - 1000
EP - 1013
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 6
ER -