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Mechanism of mast cell deficiency in mutant mice of mi/mi genotype: an analysis by co-culture of mast cells and fibroblasts.

Abstract
Mutant mice of mi/mi genotype are osteopetrotic and are deficient in mast cells. The osteopetrosis of mi/mi mice can be cured by bone marrow transplantation from congenic normal (+/+) mice, and therefore, the cause of the osteopetrosis is attributed to a defect of osteoclasts. Since both osteoclasts and mast cells are the progeny of multipotential hematopoietic stem cells, we examined whether mast cells were defective in mi/mi mice. In spite of the deficiency of mast cells in tissues of mi/mi mice, mast cells did develop when spleen cells of mi/mi mice were cultured with pokeweed mitogen-stimulated spleen cell conditioned medium (PWM-SCM). The proliferative response of cultured mast cells (CMC) derived from mi/mi mice to PWM-SCM was comparable with that of CMC from +/+ mice. In contrast, when CMC were co-cultured with the NIH/3T3 fibroblast cell line in culture medium lacking PWM-SCM, only +/+ CMC entered into the S phase of the cell cycle and were maintained; mi/mi CMC gradually disappeared. Moreover, fibroblasts derived from the skin of mi/mi mice normally supported the proliferation of +/+ CMC. Thus, the mast cell deficiency of mi/mi mice appears to be due to the inability of mi/mi mast cells to respond to the proliferative stimulus presented by fibroblasts.
AuthorsY Ebi, T Kasugai, Y Seino, H Onoue, T Kanemoto, Y Kitamura
JournalBlood (Blood) Vol. 75 Issue 6 Pg. 1247-51 (Mar 15 1990) ISSN: 0006-4971 [Print] United States
PMID2310824 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-3
  • Interleukin-4
Topics
  • Animals
  • Cell Division (drug effects)
  • Cells, Cultured
  • Female
  • Fibroblasts (cytology, drug effects, metabolism)
  • Genotype
  • Interleukin-3 (pharmacology)
  • Interleukin-4 (pharmacology)
  • Male
  • Mast Cells (cytology, drug effects, metabolism)
  • Mice
  • Mice, Mutant Strains (genetics)
  • Spleen (cytology)

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