This Article Full Text Full Text (PDF) Supplemental Figures Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yan, W. Articles by Matzuk, M. M. Search for Related Content PubMed PubMed Citation Articles by Yan, W. Articles by Matzuk, M. M.

Identification of Gasz, an Evolutionarily Conserved Gene Expressed Exclusively in Germ Cells and Encoding a Protein with Four Ankyrin Repeats, a Sterile- Motif, and a Basic Leucine Zipper

Departments of Pathology (W.Y., M.M.M.), Department of Molecular and Cellular Biology (M.M.M.), Department of Molecular and Human Genetics (M.M.M., K.H.B.), Department of Obstetrics and Gynecology (A.R.), Baylor College of Medicine, Houston, Texas 77030; The Jackson Laboratory (M.M.V., J.J.E.), Bar Harbor, Maine 04609

Address all correspondence and requests for reprints to: Martin M. Matzuk, M.D., Ph.D., Stuart A. Wallace Chair and Professor, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030. E-mail: mmatzuk{at}bcm.tmc.edu.

To discover causes of infertility and potential contraceptive targets, we used in silico subtraction and genomic database mining to identify conserved genes with germ cell-specific expression. In silico subtraction identified an expressed sequence tag (EST) present exclusively in a newborn mouse ovary library. The full-length cDNA sequence corresponding to this EST encodes a novel protein containing four ankyrin (ANK) repeats, a sterile- motif (SAM), and a putative basic leucine zipper (bZIP) domain. Northern blot and semiquantitative RT-PCR analyses demonstrated that the mRNA is exclusively expressed in the mouse testis and ovary. The expression sites were localized by in situ hybridization to pachytene spermatocytes in the testis and oocytes in the ovary. Immunohistochemistry showed that the novel protein is localized to the cytoplasm in pachytene spermatocytes and early spermatids, oocytes at all stages of oogenesis, and in early preimplantation embryos. Based on its germ cell-specific expression and the presence of ANK, SAM, and basic leucine zipper domains, we have termed this novel protein GASZ. The mouse Gasz gene, which consists of 13 exons and spans 60 kb, is located on chromosome 6 between the Wnt2 and cystic fibrosis transmembrane conductance regulator (Cftr) genes. Using genomic database mining, orthologous genes encoding GASZ were identified in the rat, cow, baboon, chimpanzee, and human. Phylogenetic analyses reveal that the GASZ proteins are highly conserved among these species. Human and mouse GASZ proteins share 85.3% amino acid identity, and human and chimpanzee GASZ proteins differ by only 3 out of 475 amino acids. In humans, the GASZ gene resides on chromosome 7 and is similarly composed of 13 exons. Because both ANK repeats and the SAM domain function as protein-protein interaction modules that mediate signal transduction cascades in some systems, GASZ may represent an important cytoplasmic signal transducer that mediates protein-protein interactions during germ cell maturation in both males and females and during preimplantation embryogenesis.

This article has been cited by other articles:

				Y.-H. Lin, Y.-M. Lin, Y.-Y. Wang, I-S. Yu, Y.-W. Lin, Y.-H. Wang, C.-M. Wu, H.-A. Pan, S.-C. Chao, P. H. Yen, et al. The Expression Level of Septin12 Is Critical for Spermiogenesis Am. J. Pathol., May 1, 2009; 174(5): 1857 - 1868. [Abstract] [Full Text] [PDF]

				N. P. Blackledge, C. J. Ott, A. E. Gillen, and A. Harris An insulator element 3' to the CFTR gene binds CTCF and reveals an active chromatin hub in primary cells Nucleic Acids Res., March 1, 2009; 37(4): 1086 - 1094. [Abstract] [Full Text] [PDF]

				Y. Choi, D. Yuan, and A. Rajkovic Germ Cell-Specific Transcriptional Regulator Sohlh2 Is Essential for Early Mouse Folliculogenesis and Oocyte-Specific Gene Expression Biol Reprod, December 1, 2008; 79(6): 1176 - 1182. [Abstract] [Full Text] [PDF]

				N. Mise, T. Fuchikami, M. Sugimoto, S. Kobayakawa, F. Ike, T. Ogawa, T. Tada, S. Kanaya, T. Noce, and K. Abe Differences and similarities in the developmental status of embryo-derived stem cells and primordial germ cells revealed by global expression profiling. Genes Cells, August 1, 2008; 13(8): 863 - 877. [Abstract] [Full Text] [PDF]

				Y.-N. Lin, A. Roy, W. Yan, K. H. Burns, and M. M. Matzuk Loss of Zona Pellucida Binding Proteins in the Acrosomal Matrix Disrupts Acrosome Biogenesis and Sperm Morphogenesis Mol. Cell. Biol., October 1, 2007; 27(19): 6794 - 6805. [Abstract] [Full Text] [PDF]

				A. Roy, Y.-N. Lin, J. E. Agno, F. J. DeMayo, and M. M. Matzuk Absence of tektin 4 causes asthenozoospermia and subfertility in male mice FASEB J, April 1, 2007; 21(4): 1013 - 1025. [Abstract] [Full Text] [PDF]

				S. Wang, H. Zheng, Y. Esaki, F. Kelly, and W. Yan Cullin3 Is a KLHL10-Interacting Protein Preferentially Expressed During Late Spermiogenesis Biol Reprod, January 1, 2006; 74(1): 102 - 108. [Abstract] [Full Text] [PDF]

				J. H. Brown, M.-T. Bihoreau, S. Hoffmann, B. Kranzlin, I. Tychinskaya, N. Obermuller, D. Podlich, S. N. Boehn, P. J. Kaisaki, N. Megel, et al. Missense Mutation in Sterile {alpha} Motif of Novel Protein SamCystin is Associated with Polycystic Kidney Disease in (cy/+) Rat J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3517 - 3526. [Abstract] [Full Text] [PDF]

				J.-L. Jin, A. M. O'Doherty, S. Wang, H. Zheng, K. M. Sanders, and W. Yan Catsper3 and Catsper4 Encode Two Cation Channel-Like Proteins Exclusively Expressed in the Testis Biol Reprod, December 1, 2005; 73(6): 1235 - 1242. [Abstract] [Full Text] [PDF]

				W. Yan, L. Ma, P. Stein, S. A. Pangas, K. H. Burns, Y. Bai, R. M. Schultz, and M. M. Matzuk Mice Deficient in Oocyte-Specific Oligoadenylate Synthetase-Like Protein OAS1D Display Reduced Fertility Mol. Cell. Biol., June 1, 2005; 25(11): 4615 - 4624. [Abstract] [Full Text] [PDF]

				A. M Johnston, G. Naselli, H. Niwa, T. Brodnicki, L. C Harrison, and L. J. Gonez Harp (harmonin-interacting, ankyrin repeat-containing protein), a novel protein that interacts with harmonin in epithelial tissues Genes Cells, October 1, 2004; 9(10): 967 - 982. [Abstract] [Full Text] [PDF]

				D. Zink, M. D. Amaral, A. Englmann, S. Lang, L. A. Clarke, C. Rudolph, F. Alt, K. Luther, C. Braz, N. Sadoni, et al. Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei J. Cell Biol., September 13, 2004; 166(6): 815 - 825. [Abstract] [Full Text] [PDF]

				W. Yan, L. Ma, C. A. Zilinski, and M. M. Matzuk Identification and Characterization of Evolutionarily Conserved Pufferfish, Zebrafish, and Frog Orthologs of GASZ Biol Reprod, June 1, 2004; 70(6): 1619 - 1625. [Abstract] [Full Text] [PDF]

				W. Yan, L. Ma, K. H. Burns, and M. M. Matzuk Haploinsufficiency of kelch-like protein homolog 10 causes infertility in male mice PNAS, May 18, 2004; 101(20): 7793 - 7798. [Abstract] [Full Text] [PDF]

				J. D. Hennebold Characterization of the ovarian transcriptome through the use of differential analysis of gene expression methodologies Hum. Reprod. Update, May 1, 2004; 10(3): 227 - 239. [Abstract] [Full Text] [PDF]

				M. Otala, L. Suomalainen, M. O. Pentikainen, P. Kovanen, M. Tenhunen, K. Erkkila, J. Toppari, and L. Dunkel Protection from Radiation-Induced Male Germ Cell Loss by Sphingosine-1-Phosphate Biol Reprod, March 1, 2004; 70(3): 759 - 767. [Abstract] [Full Text] [PDF]

				J. Penttinen, D. A. Pujianto, P. Sipila, I. Huhtaniemi, and M. Poutanen Discovery in Silico and Characterization in Vitro of Novel Genes Exclusively Expressed in the Mouse Epididymis Mol. Endocrinol., November 1, 2003; 17(11): 2138 - 2151. [Abstract] [Full Text] [PDF]

				N. Minami, A. Aizawa, R. Ihara, M. Miyamoto, A. Ohashi, and H. Imai Oogenesin Is a Novel Mouse Protein Expressed in Oocytes and Early Cleavage-Stage Embryos Biol Reprod, November 1, 2003; 69(5): 1736 - 1742. [Abstract] [Full Text] [PDF]

				W. Yan, L. Ma, K. H. Burns, and M. M. Matzuk HILS1 is a spermatid-specific linker histone H1-like protein implicated in chromatin remodeling during mammalian spermiogenesis PNAS, September 2, 2003; 100(18): 10546 - 10551. [Abstract] [Full Text] [PDF]

				H. Iida, A. Urasoko, M. Doiguchi, T. Mori, K. Toshimori, and Y. Shibata Complementary DNA Cloning and Characterization of Rat spergen-2, a Spermatogenic Cell-Specific Gene 2 Encoding a 56-Kilodalton Nuclear Protein Bearing Ankyrin Repeat Motifs Biol Reprod, August 1, 2003; 69(2): 421 - 429. [Abstract] [Full Text] [PDF]

				W. Yan, A. H. Assadi, A. Wynshaw-Boris, G. Eichele, M. M. Matzuk, and G. D. Clark Previously uncharacterized roles of platelet-activating factor acetylhydrolase 1b complex in mouse spermatogenesis PNAS, June 10, 2003; 100(12): 7189 - 7194. [Abstract] [Full Text] [PDF]

				Y. Kikkawa, H. Shitara, S. Wakana, Y. Kohara, T. Takada, M. Okamoto, C. Taya, K. Kamiya, Y. Yoshikawa, H. Tokano, et al. Mutations in a new scaffold protein Sans cause deafness in Jackson shaker mice Hum. Mol. Genet., March 1, 2003; 12(5): 453 - 461. [Abstract] [Full Text] [PDF]

				N. Suzumori, K. H. Burns, W. Yan, and M. M. Matzuk RFPL4 interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway PNAS, January 21, 2003; 100(2): 550 - 555. [Abstract] [Full Text] [PDF]