Developmental expression of latent transforming growth factor β binding protein 2 and its requirement early in mouse development

J. Michael Shipley, Robert P. Mecham, Erika Maus, Jeffrey Bonadio, Joel Rosenbloom, Ronald T. McCarthy, Mary L. Baumann, Cheryl Frankfater, Fernando Segade, Steven D. Shapiro

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Abstract

Latent transforming growth factor β (TGF-β) binding protein 2 (LTBP-2) is an integral component of elastin-containing microfibrils. We studied the expression of LTBP-2 in the developing mouse and rat by in situ hybridization, using tropoelastin expression as a marker of tissues participating in elastic fiber formation. LTBP-2 colocalized with tropoelastin within the perichondrium, lung, dermis, large arterial vessels, epicardium, pericardium, and heart valves at various stages of rodent embryonic development. Both LTBP-2 and tropoelastin expression were seen throughout the lung parenchyma and within the cortex of the spleen in the young adult mouse. In the testes, LTBP-2 expression was seen within lumenal cells of the epididymis in the absence of tropoelastin. Collectively, these results imply that LTBP-2 plays a structural role within elastic fibers in most cases. To investigate its importance in development, mice with a targeted disruption of the Ltbp2 gene were generated. Ltbp2(-/-) mice die between embryonic day 3.5 (E3.5) and 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-β 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.

Original languageEnglish
Pages (from-to)4879-4887
Number of pages9
JournalMolecular and cellular biology
Volume20
Issue number13
DOIs
StatePublished - Jul 1 2000

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    Shipley, J. M., Mecham, R. P., Maus, E., Bonadio, J., Rosenbloom, J., McCarthy, R. T., Baumann, M. L., Frankfater, C., Segade, F., & Shapiro, S. D. (2000). Developmental expression of latent transforming growth factor β binding protein 2 and its requirement early in mouse development. Molecular and cellular biology, 20(13), 4879-4887. https://doi.org/10.1128/MCB.20.13.4879-4887.2000