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Molecular and Cellular Biology, July 2000, p. 4879-4887, Vol. 20, No. 13
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
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Developmental Expression of Latent Transforming
Growth Factor
Binding Protein 2 and Its Requirement Early in
Mouse Development
(TGF-
) 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-
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.
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