Developmental expression of latent transforming growth factor beta bindingprotein 2 and its requirement early in mouse development

Latent transforming growth factor beta (TGF-beta) binding protein 2 (LTBP-2 ) is an integral component of elastin-containing microfibrils. We studied t he expression of LTBP-2 in the developing mouse and rat by in situ hybridiz ation, using tropoelastin expression as a marker of tissues participating i n elastic fiber formation. LTBP-2 colocalized with tropoelastin within the perichondrium, lung, dermis, large arterial vessels, epicardium, pericardiu m, and heart valves at various stages of rodent embryonic development. Both LTBP-2 and tropoelastin expression were seen throughout the lung parenchym a and within the cortex of the spleen in the young adult mouse. In the test es, LTBP-2 expression was seen within lumenal cells of the epididymis in th e absence of tropoelastin. Collectively, these results imply that LTBP-2 pl ays a structural role within elastic fibers in most cases. To investigate i ts importance in development, mice with a targeted disruption of the Ltbp2 gene were generated. Ltbp2(-/-) mice die between embryonic day 3.5 (E3.5) a nd E6.5. LTBP-2 expression was not detected by in situ hybridization in E6. 5 embryos but was detected in E3.5 blastocysts by reverse transcription-PCR . These results are not consistent with the phenotypes of TGF-beta knockout mice or mice with knockouts of other elastic fiber proteins, implying that LTBP-2 performs a yet undiscovered function in early development, perhaps in implantation.