X inactivation and somatic cell selection rescue female mice carrying a Piga-null mutation

Peter Keller, Gabi Tremml, Vittorio Rosti, Monica Bessler

Research output: Contribution to journalArticlepeer-review


A somatic mutation in the X linked PIGA gene is responsible for the deficiency of glycosyl phosphatidylinositol (GPI)-anchored proteins on blood cells from patients with paroxysmal nocturnal hemoglobinuria. No inherited form of GPI-anchor deficiency has been described. Because conventional Piga gene knockout is associated with high embryonic lethality in chimeric mice, we used the Cre/loxP system. We generated mice in which two loxP sites flank part of Piga exon 2. After crossbreeding with female mice of the EIIa-cre strain, the floxed allele undergoes Cre-mediated recombination with high efficiency during early embryonic development. Because of X chromosome inactivation, female offspring are mosaic for cells that express or lack GPI- linked proteins. Analysis of mosaic mice showed that in heart, lung, kidney, brain, and liver, mainly wild-type Piga is active, suggesting that these tissues require GPI-linked proteins. The salient exceptions were spleen, thymus, and red blood cells, which had almost equal numbers of cells expressing the wild-type or the recombined allele, implying that GPI-linked proteins are not essential for the derivation of these tissues. PIGA(-) cells had no growth advantage, suggesting that other factors are needed for their clonal dominance in patients with paroxysmal nocturnal hemoglobinuria.

Original languageEnglish
Pages (from-to)7479-7483
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
Publication statusPublished - Jun 22 1999


  • Cre
  • Glycosyl phosphatidylinositol
  • loxP
  • Paroxysmal nocturnal hemoglobinuria
  • Xp22

ASJC Scopus subject areas

  • Genetics
  • General

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