A tissue-specific knockout reveals that Gata1 is not essential for Sertoli cell function in the mouse

The transcription factor Gata1 is essential for the development of erythroid cells. Consequently, Gata1 null mutants die in utero due to severe anaemia. Outside the haematopoietic system, Gata1 is only expressed in the Sertoli cells of the testis. To elucidate the function of Gata1 in the testis, we made a Sertoli cell-specific knockout of the Gata1 gene in the mouse. We deleted a normally functioning 'floxed' Gata1 gene in pre-Sertoli cells in vivo through the expression of Cre from a transgene driven by the Desert Hedgehog promoter. Surprisingly, Gata1 null testes developed to be morphologically normal, spermatogenesis was not obviously affected and expression levels of putative Gata1 target genes, and other Gata factors, were not altered. We conclude that expression of Gata1 in Sertoli cells is not essential for testis development or spermatogenesis in the mouse

Enforced expression of GATA-3 during T cell development inhibits maturation of CD8 single-positive cells and induces thymic lymphoma in transgenic mice

The zinc finger transcription factor GATA-3 is of critical importance for early T cell development and commitment of Th2 cells. To study the role of GATA-3 in early T cell development, we analyzed and modified GATA-3 expression in vivo. In mice carrying a targeted insertion of a lacZ reporter on one allele, we found that GATA-3 transcription in CD4(+)CD8(+) double-positive thymocytes correlated with the onset of positive selection events, i.e., TCRalphabeta up-regulation and CD69 expression. LacZ expression remained high ( approximately 80% of cells) during maturation of CD4 single-positive (SP) cells in the thymus, but in developing CD8 SP cells the fraction of lacZ-expressing cells decreased to <20%. We modified this pattern by enforced GATA-3 expression driven by the CD2 locus control region, which provides transcription of GATA-3 throughout T cell development. In two independent CD2-GATA3-transgenic lines, approximately 50% of the mice developed thymic lymphoblastoid tumors that were CD4(+)CD8(+/low) and mostly CD3(+). In tumor-free CD2-GATA3-transgenic mice, the total numbers of CD8 SP cells in the thymus were within normal ranges, but their maturation was hampered, as indicated by increased apoptosis of CD8 SP cells and a selective deficiency of mature CD69(low)HSA(low) CD8 SP cells. In the spleen and lymph nodes, the numbers of CD8(+) T cells were significantly reduced. These findings indicate that GATA-3 supports development of the CD4 lineage and inhibits maturation of CD8 SP cells in the thymus

GATA-3 is involved in the development of serotonergic neurons in the caudal raphe nuclei

Abstract The GATA-3 transcription factor shows a specific and restricted expression pattern in the developing and adult mouse brain. In the present study we investigated the role of GATA-3 in the caudal raphe system, which is known to operate as a modulator of motor activity. We demonstrate that virtually all neurons in the caudal raphe nuclei that express GATA-3 also produce serotonin. Absence of GATA-3, as analyzed in chimeric -/- mice, affects the cytoarchitecture of serotonergic neurons in the caudal raphe nuclei. As a result the chimeras show a serious defect in their locomotor performance on a rotating rod. In sum, we conclude that GATA-3 plays a major role in the development of the serotonergic neurons of the caudal raphe nuclei, and that it is crucial for their role in locomotion

Zfp-37 is a member of the KRAB zinc finger gene family and is expressed in neurons of the developing and adult CNS.

The murine Zfp-37 gene encodes a protein with 12 zinc fingers at its C-terminus (Nelki et al., 1990, Nucleic Acids Res. 18: 3655; Burke and Wolgemuth, 1992, Nucleic Acids Res. 20: 2827-2834). Contrary to the published data, our Northern blot analysis demonstrates not only that the Zfp-37 gene is expressed as 2.3, 2.6, and 4.2 kb mRNAs in testis, but also that there is a 3.7-kb message in the adult mouse brain. Using a partial cDNA as a probe, we have isolated a brain-specific Zfp-37 cDNA clone of 3.3 kb, whose sequence was extended to full length using 5' end RACE. This revealed that the 3.7-kb mRNA is in fact a collection of transcripts with heterogenous 5' ends. Comparison of cDNA and genomic sequences shows that the Zfp-37 gene is spread over a region of approximately 20 kb and consists of six exons, the large 3' end exon containing the complete zinc finger domain, and 3' UTR. Our data show that the Zfp-37 gene utilizes different promoters, alternative splicing, and differential polyadenylation to generate the distinct transcripts of brain and testis. Several protein isoforms are encoded by these mRNAs, some of which contain a truncated form of a conserved domain (Kruppel-associated box) found in other zinc finger genes. In situ hybridization analysis of postnatal brain sections indicates that the Zfp-37 gene is expressed in all neurons of the central nervous system. Together, these results suggest that ZFP-37 is a transcriptional regulator predominantly present in postmitotic cells from two different lineages

A tissue-specific knockout reveals that Gata1 is not essential for Sertoli cell function in the mouse

The transcription factor Gata1 is essential for the development of erythroid cells. Consequently, Gata1 null mutants die in utero due to severe anaemia. Outside the haematopoietic system, Gata1 is only expressed in the Sertoli cells of the testis. To elucidate the function of Gata1 in the testis, we made a Sertoli cell-specific knockout of the Gata1 gene in the mouse. We deleted a normally functioning ‘floxed’ Gata1 gene in pre-Sertoli cells in vivo through the expression of Cre from a transgene driven by the Desert Hedgehog promoter. Sur prisingly, Gata1 null testes developed to be morphologically normal, spermatogenesis was not obviously affected and expression levels of putative Gata1 target genes, and other Gata factors, were not altered. We conclude that expression of Gata1 in Sertoli cells is not essential for testis development or spermatogenesis in the mouse