Disease relevance of Ltbp3

• To explore LTBP function in vivo, we created an Ltbp-3(-/-) mouse that has developmental emphysema with decreased septation in terminal alveoli [1].
• Taken together, these results indicate that the Ltbp-3-/- high bone mass phenotype was due to a defect in bone resorption [2].
• Ltbp-3-/- animals developed craniofacial abnormalities due to early ossification of the skull base synchondroses and displayed reduced body size [2].

High impact information on Ltbp3

• These observations give support to the notion that LTBP-3 is important for the control of TGF-beta action [3].
• Bone abnormalities in latent TGF-[beta] binding protein (Ltbp)-3-null mice indicate a role for Ltbp-3 in modulating TGF-[beta] bioavailability [3].
• Finally, we note that the LTBP-3 gene was recently localized to a distinct genetic locus (Li, X., Yin, W., Perez-Jurado, L., Bonadio, J., and Francke, U. (1995) Mamm. Genome 6, 42-45) [4].
• The osteoblast numbers and mineral apposition rates were decreased in Ltbp-3-/- mice, whereas the osteoclast numbers were similar in null and wild type mice [2].
• Compared with wild-type or heterozygous littermates, the basooccipital-basosphenoid synchondrosis of Ltbp-3 null mice contained increased numbers of hypertrophic chondrocytes [5].

Biological context of Ltbp3

• These results indicate that in the absence of Ltbp-3, a temporary decrease in TGF-beta signaling in the lungs at days 4 to 6 alters cell proliferation, correlating with inhibition of septation and developmental emphysema [1].
• Alternative splicing of LTBP-3 [6].
• The amino acid sequence derived from the MkLTBP-3 gene shared 98.6% identity with human LTBP-3 and 86.7% identity with mouse LTBP-3 amino acid sequences [7].

Associations of Ltbp3 with chemical compounds

• The second TGF-bp repeat of LTBP-3 is unusual in that it has 9 cysteine residues instead of 8, and our results provide the first evidence that a TGF-bp repeat with an odd number of cysteine residues can covalently bind latent TGF-beta 1 [8].

Physical interactions of Ltbp3

• There is indirect evidence that LTBP-2 and LTBP-3 also bind the latent TGF-beta complex, but the nature and location of the binding interaction are unknown [8].

Other interactions of Ltbp3

• We have used immunoprecipitation, SDS-PAGE, and autoradiography to characterize the association between mouse LTBP-3 and the small latent TGF-beta 1 complex [8].
• We report that the second and third TGF-bp repeats of LTBP-3 covalently bind the latent complex, and we show a similar capability for the homologous TGF-bp repeats of mouse LTBP-2 [8].

Analytical, diagnostic and therapeutic context of Ltbp3

• To examine the role of the Ltbp-3, we made an Ltbp-3-null mutation in the mouse by gene targeting [3].

References