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.