title: Bcl-2 and Bcl-XL are indispensable for the late phase of mast cell development from mouse embryonic stem cells.
abstract: OBJECTIVE
  The aim of this study was to determine the importance of the prosurvival factors Bcl-2 and Bcl-XL for mast cell development and survival.
  
  
  METHODS
  bcl-x(-/-) and bcl-2(-/-) mouse embryonic stem cells were maintained in medium supplemented with either interleukin (IL)-3 or IL-3 in combination with stem cell factor (SCF) to favor mast cell development. The development of Bcl-2 family deficient embryonic stem cell-derived mast cells (ESMCs) was monitored and Bcl-2 family gene expression and cell numbers were analyzed.
  
  
  RESULTS
  Deficiency in either bcl-x or bcl-2 totally inhibited the development of ESMCs when IL-3 alone was used as a mast cell growth factor. Intriguingly, when IL-3 was used in combination with SCF, the ESMCs developed normally the first 2 weeks but thereafter the cell numbers dropped drastically. The remaining ESMCs express mouse mast cell protease 1, suggesting a mucosal-like phenotype. ESMCs lacking bcl-x or bcl-2 exhibited strong expression of A1, another prosurvival Bcl-2 family member.
  
  
  CONCLUSIONS
  For the first time we provide direct evidence that both bcl-x and bcl-2 are indispensable for mast cell survival during the late phase of their development.
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Christine.Moller@ki.se
authors.forename: Christine
authors.initials: C
authors.lastname: Möller
authors.forename: Mats
authors.initials: M
authors.lastname: Karlberg
authors.forename: Magnus
authors.initials: M
authors.lastname: Abrink
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
authors.forename: Noboru
authors.initials: N
authors.lastname: Motoyama
authors.forename: Gunnar
authors.initials: G
authors.lastname: Nilsson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005838:Genotype; D007377:Interleukin-3 / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051020:bcl-X Protein / Q000235:genetics / Q000502:physiology*
chemical_list: C096816:BCL2-related protein A1; C494812:Bcl2l1 protein, mouse; D007377:Interleukin-3; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019089:Stem Cell Factor; D051020:bcl-X Protein; C052617:Bcl2 protein, mouse