The TGF-βs are multifunctional proteins whose activities are believed to be controlled by interaction with the latent TGF-β binding proteins (LTBPs). In spite of substantial effort, the precise in vivo significance of this interaction remains unknown. To examine the role of the Ltbp-3, we made an Ltbp-3-null mutation in the mouse by gene targeting. Homozygous mutant animals develop cranio-facial malformations by day 10. At 2 mo, there is a pronounced rounding of the cranial vault, extension of the mandible beyond the maxilla, and kyphosis. Histological examination of the skulls from null animals revealed ossification of the synchondroses within 2 wk of birth, in contrast to the wild-type synchondroses, which never ossify. Between 6 and 9 mo of age, mutant animals also develop osteosclerosis and osteoarthritis. The pathological changes of the Ltbp-3-null mice are consistent with perturbed TGF-β signaling in the skull and long bones. These observations give support to the notion that LTBP-3 is important for the control of TGF-β action. Moreover, the results provide the first in vivo indication for a role of LTBP in modulating TGF-β bioavailability.
CITATION STYLE
Dabovic, B., Chen, Y., Colarossi, C., Obata, H., Zambuto, L., Perle, M. A., & Rifkin, D. B. (2002). Bone abnormalities in latent TGF-β binding protein (Ltbp)-3-null mice indicate a role for Ltbp-3 in modulating TGF-β bioavailability. Journal of Cell Biology, 156(2), 227–232. https://doi.org/10.1083/jcb.200111080
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