CRISPR/Cas9-mediated generation of human embryonic stem cell sub-lines with HPRT1 gene knockout to model Lesch Nyhan disease

Stem Cell Res. 2023 Sep:71:103144. doi: 10.1016/j.scr.2023.103144. Epub 2023 Jun 15.

Abstract

Lesch-Nyhan disease (LND) is a X-linked genetic disease affecting boys characterized by complex neurological and neuropsychiatric symptoms. LND is caused by loss of function mutations in the HPRT1 gene leading to decrease activity of hypoxanthine-guanine phosphoribosyl transferase enzyme (HGPRT) and altered purine salvage pathway (Lesch and Nyhan, 1964). This study describes the generation of isogenic clones with deletions in HPRT1 produced from one male human embryonic stem cell line using CRISPR/Cas9 strategy. Differentiation of these cells into different neuronal subtypes will help elucidating the neurodevelopmental events leading to LND and develop therapeutic strategies for this devastating neurodevelopmental disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems / genetics
  • Gene Knockout Techniques
  • Human Embryonic Stem Cells* / metabolism
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Hypoxanthine Phosphoribosyltransferase / metabolism
  • Lesch-Nyhan Syndrome* / genetics
  • Lesch-Nyhan Syndrome* / metabolism
  • Male

Substances

  • Hypoxanthine Phosphoribosyltransferase