caa a22 4500 397575327 CHVBK 20180308164854.0 cr unu---uuuuu 161202e199605 xx s 000 0 eng 10.1093/hmg/5.5.639 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.5.639 Expression of the Von Hippel—Lindau Disease Tumour Suppressor Gene during Human Embryogenesis [Elektronische Daten] [Frances M. Richards, Paul N. Schofield, Stewart Fleming, Eamonn R. Maher] The von Hippel-Lindau (VHL) disease product is thought to down-regulate transcription by antagonizing elongin-enhanced transcriptional elongation. Germline VHL gene mutations predispose to the development of retinal, cerebellar and spinal haemangioblastomas, renal cell carcinoma and phaeochromocytoma. In addition, somatic inactivation of the VHL gene is frequent in sporadic renal cell carcinoma and haemangioblastoma. Regulation of transcript elongation is an important control mechanism for gene expression and the VHL gene might modify the expression of proto-oncogenes and growth suppressor genes during embryogenesis. We therefore investigated the expression of VHL mRNA during human embryogenesis by in situ hybridization studies at 4, 6 and 10 weeks post conception. Although VHL mRNA was expressed in all three germ layers, strong expression was noted in the central nervous system, kidneys, testis and lung. Within the kidney, VHL mRNA was differentially expressed within renal tubules suggesting that the VHL gene product may have a specific role in kidney development. Two alternatively spliced VHL mRNAs characterized by inclusion (isoform I) or exclusion (iso-form II) of exon 2 are transcribed in adult tissues. To investigate if the two isoforms are differentially expressed during embryogenesis, VHL mRNA was reverse transcribed from 13 fetal tissues (8-10 weeks gestation). The quantitative distribution of VHL mRNA within fetal tissues reflected that seen by in situ hybridization and the ratio of the two VHL isoforms was similar between tissues. Although the genes regulated by the VHL gene product have not yet been identified, our findings are compatible with the hypothesis that VHL-mediated control of transcriptional elongation may have a role in normal human development. © 1996 Oxford University Press Richards Frances M. Cambridge University Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK aut Schofield Paul N. Cambridge University Department of Anatomy, Downing Street, Cambridge CB2 3DY, UK aut Fleming Stewart Department of Pathology, University of Edinburgh, Edinburgh, UK aut Maher Eamonn R. Cambridge University Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK aut Human Molecular Genetics Oxford University Press 5/5(1996-05), 639-644 0964-6906 5:5<639 1996 5 hmg https://doi.org/10.1093/hmg/5.5.639 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.5.639 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Richards Frances M. Cambridge University Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK aut NATIONALLICENCE 700 1- Schofield Paul N. Cambridge University Department of Anatomy, Downing Street, Cambridge CB2 3DY, UK aut NATIONALLICENCE 700 1- Fleming Stewart Department of Pathology, University of Edinburgh, Edinburgh, UK aut NATIONALLICENCE 700 1- Maher Eamonn R. Cambridge University Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/5(1996-05), 639-644 0964-6906 5:5<639 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford