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Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2002, Vol. 100, No. 2, pp. 560-568 IMMUNOBIOLOGY Induced disruption of the transforming growth factor beta type II receptor gene in mice causes a lethal inflammatory disorder that is transplantable Per Levéen, Jonas Larsson, Mats Ehinger, Corrado M. Cilio, Martin Sundler, Lottie Jansson Sjöstrand, Rikard Holmdahl, and Stefan Karlsson From the Departments of Molecular Medicine and Gene Therapy, Pathology, and Medical Inflammation Research, Lund University, Sweden; and the Department of Endocrinology and Paediatrics, Malmö University Hospital, Lund University, Malmö, Sweden. Recent studies in mouse models deficient in transforming growth factor beta (TGF-) signaling have documented TGF- as one of the major regulators of immune function. TGF-1-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- type II receptor (TRII) gene to normal recipient animals. The TRII-null mutation would generate a cell autonomous phenotype that cannot be reverted by the influence of endocrine or paracrine TGF- derived from the recipient animal. We have generated conditional knockout mice in which the TRII gene is disrupted upon induction with interferon- or polyI:polyC. We show that induction of TRII 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- receptor deficiency occurred in donor animals before, or in recipient animals after transplantation. These results show that TGF- 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- signaling and the importance of TGF- to regulate immune functions. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Vitsky, J. Waire, R. Pawliuk, A. Bond, D. Matthews, E. LaCasse, M. L. Hawes, C. Nelson, S. Richards, P. A. Piepenhagen, et al. 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