Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wilms' Tumour 1 gene (WT1) is required for the correct development of the urogenital system. To examine its regulation and expression, we created several transgenic mouse lines containing a beta-galactosidase reporter driven by the human WT1 promoter. A 5 kb promoter weakly recapitulated a subset of the endogenous Wt1 expression pattern. In contrast, 470 and 280 kb YAC transgenes reproduced the correct pattern with high activity and highlighted new expression sites. Wt1 is expressed in the septum transversum revealing how its mutation causes diaphragmatic defects. Wt1 expression in the limb demarcates a zone between chondrogenic and apoptotic domains. Finally, Wt1 is expressed in mesenchymal cells derived from the coelomic epithelium. Based upon these and further data we discuss a Wt1 role in epithelial<-->mesenchymal transitions.
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PMID:YAC transgenic analysis reveals Wilms' tumour 1 gene activity in the proliferating coelomic epithelium, developing diaphragm and limb. 1034 31

The teleost fish are widely used as model organisms in vertebrate biology. The compact genome of the pufferfish, Fugu rubripes, has proven a valuable tool in comparative genome analyses, aiding the annotation of mammalian genomes and the identification of conserved regulatory elements, whilst the zebrafish is particularly suited to genetic and developmental studies. We demonstrate that a pufferfish WT1 transgene can be expressed and spliced appropriately in transgenic zebrafish, contrasting with the situation in transgenic mice. By creating both transgenic mice and transgenic zebrafish with the same construct, we show that Fugu RNA is processed correctly in zebrafish but not in mice. Furthermore, we show for the first time that a Fugu genomic construct can produce protein in transgenic zebrafish: a full-length Fugu WT1 transgene with a C-terminal beta-galactosidase fusion is spliced and translated correctly in zebrafish, mimicking the expression of the endogenous WT1 gene. These data demonstrate that the zebrafish:Fugu system is a powerful and convenient tool for dissecting both vertebrate gene regulation and gene function in vivo.
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PMID:Faithful expression of a tagged Fugu WT1 protein from a genomic transgene in zebrafish: efficient splicing of pufferfish genes in zebrafish but not mice. 1277 Dec 6

The glomerular filtration barrier separates the blood from the urinary space. Nephrin is a transmembrane protein that belongs to the immunoglobulin superfamily and is localized to the slit diaphragms that are a critical component of this filtration barrier. Mutations in the nephrin gene (NPHS1) lead to congenital Finnish nephropathy, whereas alterations in the level of nephrin expression have been identified in a wide range of acquired glomerular diseases. A 186-bp fragment from the human NPHS1 promoter is capable of directing podocyte-specific expression of a beta-galactosidase transgene when placed in front of a heterologous minimal promoter in transgenic mice. The Wilms tumor suppressor gene (WT1) is a zinc-finger-containing transcription factor that is coexpressed with NPHS1 in differentiated podocytes; gel shift binding assays demonstrate that a recombinant WT1 protein can bind and activate the 186-bp NPHS1 fragment in a sequence-specific manner. Taken together, these results suggest that WT1 may be required for regulation of the NPHS1 gene in vivo.
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PMID:WT1 activates a glomerular-specific enhancer identified from the human nephrin gene. 1550 38

Embryonic stem (ES) cells have the capacity to differentiate into all cells of the developing embryo and may provide a renewable resource for future cell replacement therapies. The addition of bone morphogenetic protein 4 (BMP4) to serum-free ES cell culture has previously been shown to induce transcription factors, signaling molecules, and cell adhesion proteins expressed during mesoderm specification of the embryo. Here, we show the dynamics of primitive streak mesoderm differentiation in ES cells is comparable between serum and serum-free embryoid body (EB) cultures, supplemented with BMP4. Furthermore, we show a delayed wave of expression of a cohort of genes (Pax2, WT1, podocalyxin, pod-1, and nephrin), which play important roles during embryonic kidney development. The paired box transcription factor, Pax2, is one of the earliest genes expressed during kidney organogenesis and is required for normal urogenital development. ES cell lines containing either a modified Pax2 promoter-lacZ or bacterial artificial chromosome-green fluorescent protein (GFP) transgene were generated, which enabled the quantitative analysis of kidney rather than neuronal Pax2 expression within EBs. Both beta-galactosidase activity and GFP expression were detected by immunohistochemical and flow cytometric analysis following 16 days of EB culture, which correlated with an increase in Pax2 transcript levels. Together, these results suggest a spontaneous kidney gene expression program develops in mature EBs grown in both serum and serum-free conditions, when supplemented with BMP4. Further, the recombinant growth factors BMP2, BMP4, and BMP7 strongly influence gene expression within mesoderm induced EBs. BMP4 promotes ventral (blood) and intermediate (kidney) mesoderm gene expression, whereas BMP2 and BMP7 promote kidney outcomes at the expense of hematopoietic commitment. This induction assay and these unique ES cell lines will be useful for the generation of mesoderm-derived cell populations with implications for future cell therapeutic/integration assays.
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PMID:In vitro differentiation of murine embryonic stem cells toward a renal lineage. 1728 99