| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
LETTER TO THE EDITOR |
Department of Genetics, Silberman Institute of Life Science, The Hebrew University, Jerusalem, Israel
Key Words. Human ES cells • Genetic diseases • Lesch-Nyhan syndrome • Homologous recombination
Correspondence: Nissim Benvenisty M.D., Ph.D., Hebrew University Department of Genetics, Institute of Life Sciences, Givat-Ram, Jerusalem 91904 Israel. Telephone: 972-2-6586774; Fax: 972-2-6584972; e-mail: nissimb{at}mail.ls.huji.ac.il
ABSTRACT
Human embryonic stem (ES) cells are pluripotent cells derived from blastocyst-stage embryos. It has been suggested that these cells should play a major role in transplantation medicine and be able to advance our knowledge in human embryology. We propose that these cells should also play a vital role in the creation of models of human disorders. This aspect would be most valuable where animal models failed to faithfully recapitulate the human phenotype. Lesch-Nyhan disease is caused by a mutation in the HPRT1 gene that triggers an overproduction of uric acid, causing gout-like symptoms and urinary stones, in addition to neurological disorders. Due to biochemical differences between humans and rodents, a mouse lacking the HPRT expression will fail to accumulate uric acid. In this research we demonstrate a model for Lesch-Nyhan disease by mutating the HPRT1 gene in human ES cells using homologous recombination. We have verified the mutation in the HPRT1 allele at the DNA and RNA levels. By using selection media, we show that HPRT1 activity is abolished in the mutant cells, and the HPRT1–cells show a higher rate of uric acid accumulation than the wild-type cells. Therefore, these cells recapitulate to some extent the characteristics of Lesch-Nyhan syndrome and can help researchers further investigate this genetic disease and analyze drugs that will prevent the onset of its symptoms. We therefore suggest that human diseases may be modeled using human ES cells.
This article has been cited by other articles:
|
|
 |
|
  R. P. Davis, E. S. Ng, M. Costa, A. K. Mossman, K. Sourris, A. G. Elefanty, and E. G. Stanley Targeting a GFP reporter gene to the MIXL1 locus of human embryonic stem cells identifies human primitive streak-like cells and enables isolation of primitive hematopoietic precursors Blood, February 15, 2008; 111(4): 1876 - 1884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Smith, S. Maguire, L. A. Davis, M. Alexander, F. Yang, S. Chandran, C. ffrench-Constant, and R. A. Pedersen Robust, Persistent Transgene Expression in Human Embryonic Stem Cells Is Achieved with AAVS1-Targeted Integration Stem Cells, February 1, 2008; 26(2): 496 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Xia, M. Ayala, B. R. Thiede, and S.-C. Zhang In Vitro- and In Vivo-Induced Transgene Expression in Human Embryonic Stem Cells and Derivatives Stem Cells, February 1, 2008; 26(2): 525 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Senju, H. Suemori, H. Zembutsu, Y. Uemura, S. Hirata, D. Fukuma, H. Matsuyoshi, M. Shimomura, M. Haruta, S. Fukushima, et al. Genetically Manipulated Human Embryonic Stem Cell-Derived Dendritic Cells with Immune Regulatory Function Stem Cells, November 1, 2007; 25(11): 2720 - 2729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Lensch and G. Q. Daley Scientific and clinical opportunities for modeling blood disorders with embryonic stem cells Blood, April 1, 2006; 107(7): 2605 - 2612. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| STEM CELLS | THE ONCOLOGIST | CME | ALPHAMED PRESS JOURNALS |
