Expression of Human Glucocerebrosidase in Long-Term Reconstituted Mice Following Retroviral-Mediated Gene Transfer into Hematopoietic Stem Cells

Pamela H. Correll, Yvonne Kew, Leland K. Perry, Roscoe O. Brady, John K. Fink, Stefan Karlsson

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

A retroviral vector (GTN) in which the glucocerebrosidase (GCase) cDNA is driven by the Moloney murine leukemia virus (Mo-MuLV) long terminal repeat (LTR) was tested for transfer efficiency and expression of the GCase gene in long-term reconstituted mice. Eleven W/Wv mice were transplanted with unselected GTN-infected bone marrow cells and 10 of these mice were analyzed 3 months later. Seven of these 10 mice (70%) contained the intact proviral genome in bone marrow, spleen, and thymus. Of these 7, 3 mice contained a high-copy number of the provirus in all the hematopoietic tissues tested. The mice contained anywhere from one to four proviral integration sites that were the same in all three tissues, indicating that these mice have been repopulated by one or more transduced multipotential hematopoietic stem cells. Five months after transplantation, bone marrow from the eleventh mouse was transplanted into secondary recipient animals. The secondary recipients contained the intact proviral genome in the bone marrow, spleen, thymus, and macrophages 4 months after the secondary transplantation. This further supports the conclusion that hematopoietic stem cells have indeed been targeted. Human GCase RNA was detected in all 7 mice containing the proviral DNA. These results demonstrate expression of the human GCase gene in the progeny of repopulating hematopoietic stem cells of mice following gene transfer.

Original languageEnglish (US)
Pages (from-to)277-287
Number of pages11
JournalHuman Gene Therapy
Volume1
Issue number3
DOIs
StatePublished - Oct 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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