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Induced disruption of the transforming growth factor beta type II receptor gene in mice causes a lethal inflammatory disorder that is transplantable.

Levéen, Per LU ; Larsson, Jonas LU ; Ehinger, Mats LU ; Cilio, Corrado LU ; Sundler, Martin; Jansson Sjöstrand, Lottie LU ; Holmdahl, Rikard LU and Karlsson, Stefan LU (2002) In Blood 100(2). p.560-568
Abstract
Recent studies in mouse models deficient in transforming growth factor beta (TGF-beta) signaling have documented TGF-beta as one of the major regulators of immune function. TGF-beta1-null animals demonstrated massive autoimmune inflammation affecting multiple organs, but attempts to transfer the phenotype to normal animals by bone marrow transplantation only resulted in minor inflammatory lesions. We wanted to ask whether a lethal inflammatory phenotype would develop following transplantation of bone marrow deficient for the TGF-beta type II receptor (TbetaRII) gene to normal recipient animals. The TbetaRII-null mutation would generate a cell autonomous phenotype that cannot be reverted by the influence of endocrine or paracrine TGF-beta... (More)
Recent studies in mouse models deficient in transforming growth factor beta (TGF-beta) signaling have documented TGF-beta as one of the major regulators of immune function. TGF-beta1-null animals demonstrated massive autoimmune inflammation affecting multiple organs, but attempts to transfer the phenotype to normal animals by bone marrow transplantation only resulted in minor inflammatory lesions. We wanted to ask whether a lethal inflammatory phenotype would develop following transplantation of bone marrow deficient for the TGF-beta type II receptor (TbetaRII) gene to normal recipient animals. The TbetaRII-null mutation would generate a cell autonomous phenotype that cannot be reverted by the influence of endocrine or paracrine TGF-beta derived from the recipient animal. We have generated conditional knockout mice in which the TbetaRII gene is disrupted upon induction with interferon-alphabeta or polyI:polyC. We show that induction of TbetaRII gene disruption in these mice by polyI:polyC results in a lethal inflammatory disease. Importantly, bone marrow from conditional knockout mice transferred to normal recipent mice caused a similar lethal inflammation, regardless of whether induction of TGF-beta receptor deficiency occurred in donor animals before, or in recipient animals after transplantation. These results show that TGF-beta signaling deficiency within cells of hematopoietic origin is sufficient to cause a lethal inflammatory disorder in mice. This animal model provides an important tool to further clarify the pathogenic mechanisms in animals deficient for TGF-beta signaling and the importance of TGF-beta to regulate immune functions. (Blood. 2002;100:560-568) (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
100
issue
2
pages
560 - 568
publisher
American Society of Hematology
external identifiers
  • wos:000176741200025
  • pmid:12091349
  • scopus:0037100520
ISSN
1528-0020
language
English
LU publication?
yes
id
b19a9133-e0df-4622-9e31-a4335a032ff4 (old id 109086)
alternative location
http://bloodjournal.hematologylibrary.org/cgi/content/full/100/2/560
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12091349&dopt=Abstract
date added to LUP
2007-07-11 12:38:52
date last changed
2017-12-10 03:38:56
@article{b19a9133-e0df-4622-9e31-a4335a032ff4,
  abstract     = {Recent studies in mouse models deficient in transforming growth factor beta (TGF-beta) signaling have documented TGF-beta as one of the major regulators of immune function. TGF-beta1-null animals demonstrated massive autoimmune inflammation affecting multiple organs, but attempts to transfer the phenotype to normal animals by bone marrow transplantation only resulted in minor inflammatory lesions. We wanted to ask whether a lethal inflammatory phenotype would develop following transplantation of bone marrow deficient for the TGF-beta type II receptor (TbetaRII) gene to normal recipient animals. The TbetaRII-null mutation would generate a cell autonomous phenotype that cannot be reverted by the influence of endocrine or paracrine TGF-beta derived from the recipient animal. We have generated conditional knockout mice in which the TbetaRII gene is disrupted upon induction with interferon-alphabeta or polyI:polyC. We show that induction of TbetaRII gene disruption in these mice by polyI:polyC results in a lethal inflammatory disease. Importantly, bone marrow from conditional knockout mice transferred to normal recipent mice caused a similar lethal inflammation, regardless of whether induction of TGF-beta receptor deficiency occurred in donor animals before, or in recipient animals after transplantation. These results show that TGF-beta signaling deficiency within cells of hematopoietic origin is sufficient to cause a lethal inflammatory disorder in mice. This animal model provides an important tool to further clarify the pathogenic mechanisms in animals deficient for TGF-beta signaling and the importance of TGF-beta to regulate immune functions. (Blood. 2002;100:560-568)},
  author       = {Levéen, Per and Larsson, Jonas and Ehinger, Mats and Cilio, Corrado and Sundler, Martin and Jansson Sjöstrand, Lottie and Holmdahl, Rikard and Karlsson, Stefan},
  issn         = {1528-0020},
  language     = {eng},
  number       = {2},
  pages        = {560--568},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Induced disruption of the transforming growth factor beta type II receptor gene in mice causes a lethal inflammatory disorder that is transplantable.},
  volume       = {100},
  year         = {2002},
}