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Molecular and Cellular Biology, July 2000, p. 4879-4887, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Developmental Expression of Latent Transforming Growth Factor beta  Binding Protein 2 and Its Requirement Early in Mouse Development

J. Michael Shipley,1,* Robert P. Mecham,2 Erika Maus,1 Jeffrey Bonadio,3 Joel Rosenbloom,4 Ronald T. McCarthy,5 Mary L. Baumann,5 Cheryl Frankfater,1 Fernando Segade,2 and Steven D. Shapiro2,5

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Barnes-Jewish Hospital at Washington University School of Medicine1 and Departments of Cell Biology and Physiology2 and Pediatrics,5 Washington University School of Medicine, St. Louis, Missouri 63110; Selective Genetics, San Diego, California 921213; and University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania 191044

Received 23 February 2000/Accepted 20 March 2000

Latent transforming growth factor beta  (TGF-beta ) 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-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.

* Corresponding author. Mailing address: Washington University School of Medicine at Barnes-Jewish Hospital, Division of Pulmonary and Critical Care Medicine, 216 S. Kingshighway Blvd., St. Louis, MO 63110. Phone: (314) 454-7990. Fax: (314) 454-5919. E-mail: mshipley{at}imgate.wustl.edu.

Molecular and Cellular Biology, July 2000, p. 4879-4887, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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