title: 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.
authors.affiliation: Department of Pathology, Osaka University Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ebi
authors.forename: T
authors.initials: T
authors.lastname: Kasugai
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
authors.forename: H
authors.initials: H
authors.lastname: Onoue
authors.forename: T
authors.initials: T
authors.lastname: Kanemoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005838:Genotype; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D013154:Spleen / Q000166:cytology
chemical_list: D007377:Interleukin-3; D015847:Interleukin-4