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Growth retardation as well as spleen and thymus involution in latent TGF‐β binding protein (Ltbp)‐3 null mice
Author(s) -
Chen Yan,
Dabovic Branka,
Colarossi Cristina,
Santori Fabio R.,
Lilic Mirjana,
Vukmanovic Stanislav,
Rifkin Daniel B.
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10296
Subject(s) - spleen , medicine , thymic involution , involution (esoterism) , endocrinology , biology , corticosterone , transforming growth factor , cd8 , extracellular matrix , mutant , t cell , immune system , immunology , hormone , gene , microbiology and biotechnology , biochemistry , consciousness , neuroscience
The latent TGF‐β binding protein (LTBP)‐3 is an extracellular matrix (ECM) protein that binds the small latent complex (SLC) of TGF‐β. Disruption of the Ltbp‐3 gene by homologous recombination in mice yields mutant animals that display multiple skeletal abnormalities. In addition, these mice have retarded growth. On an inbred 129 SvEv background, half of the Ltbp‐3 mutant mice die between 3 and 4 weeks after birth. These mice show severe involution of the thymus and spleen and a sharp reduction in the numbers of CD4/CD8 double positive T‐cells in the thymus. The thymus and spleen defect is caused by elevated corticosterone levels in the serum and can be reversed by injection of aminoglutethimide (AMG), an inhibitor of steroid synthesis. This result indicates that the thymus and spleen defect is a secondary defect due to high corticosterone levels probably induced by stress of unknown etiology. J. Cell. Physiol. 196: 319–325, 2003. © 2003 Wiley‐Liss, Inc.