Effects of organ-specific loss of insulin-like growth factor-I production on murine hematopoiesis

Lisbeth A. Welniak, Michael Karas, Shoshana Yakar, Miriam R. Anver, William J Murphy, Derek LeRoith

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

To determine whether circulating insulin-like growth factor (IGF)-I has a role in hematopoiesis, we examined hematologic parameters in mice with markedly reduced serum levels resulting from a liver-specific inactivation of the IGF-I gene. These mice have normal postnatal growth and development, suggesting that local production of IGF-I can maintain anabolic effects. Liver-specific IGF-I-deficient (LID) mice were compared with control littermates with regard to hematopoietic parameters. Spleen cellularity was decreased in the LID mice compared with control mice. Spleen myeloid progenitors, as determined by colony-forming units-granulocyte/monocyte (CFU-GM) and colony-forming units-high proliferative potential (CFU-HPP), were significantly decreased in the LID mice. Immune parameters, as indicated by the absolute number of B and T cells, did not significantly differ between the knockout and control mice. In contrast to the decreased cellularity and myelopoiesis in the spleen, bone marrow cellularity was not different between the 2 groups, but the total femoral content of CFU-GM and CFU-HPP was significantly increased in the LID mice. The decrease in splenic myelopoiesis was not due to the inability of progenitors to exit the bone marrow, because CFU-GM and burst-forming units-erythroid were significantly increased in the blood of LID mice compared with normal littermates. Administration of exogenous IGF-I to the LID mice for 4 days partially restored myelopoietic parameters in the spleen. Liver production of IGF-I and, therefore, normal serum levels of this hormone, although not necessary for general organ growth and development, seems necessary for survival or transition of myeloid progenitors into the spleen.

Original languageEnglish (US)
Pages (from-to)32-39
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume10
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

Keywords

  • Growth hormone
  • Mobilization
  • Myelopoiesis
  • Progenitors

ASJC Scopus subject areas

  • Transplantation

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