Developmental expression of latent transforming growth factor beta binding protein 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 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.
Shipley
J M
JM
Department of Medicine, Barnes-Jewish Hospital at Washington University School of Medicine, St. Louis, MO 63110, USA. mshipley@imgate.wustl.edu
Mecham
R P
RP
Maus
E
E
Bonadio
J
J
Rosenbloom
J
J
McCarthy
R T
RT
Baumann
M L
ML
Frankfater
C
C
Segade
F
F
Shapiro
S D
SD
D000818:Animals; D015415:Biomarkers; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D047108:Embryonic Development; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D053779:Latent TGF-beta Binding Proteins; D008168:Lung / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D011247:Pregnancy; D051381:Rats; D014059:Tongue / Q000196:embryology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014333:Tropoelastin / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D002352:Carrier Proteins; D053779:Latent TGF-beta Binding Proteins; C509036:Ltbp2 protein, mouse; C509037:Ltbp2 protein, rat; D016212:Transforming Growth Factor beta; D014333:Tropoelastin