Abrogation of both short and long forms of latent transforming growth factor-β binding protein-1 causes defective cardiovascular development and is perinatally lethal

Matrix Biol. 2015 Apr:43:61-70. doi: 10.1016/j.matbio.2015.03.006. Epub 2015 Mar 21.


Latent transforming growth factor-β binding protein-1 (LTBP-1) is an extracellular protein that is structurally similar to fibrillin and has an important role in controlling transforming growth factor-β (TGF-β) signaling by storing the cytokine in the extracellular matrix and by being involved in the conversion of the latent growth factor to its active form. LTBP-1 is found as both short (LTBP-1S) and long (LTBP-1L) forms, which are derived through the use of separate promoters. There is controversy regarding the importance of LTBP-1L, as Ltbp1L knockout mice showed multiple cardiovascular defects but the complete null mice did not. Here, we describe a third line of Ltbp1 knockout mice generated utilizing a conditional knockout strategy that ablated expression of both L and S forms of LTBP-1. These mice show severe developmental cardiovascular abnormalities and die perinatally; thus these animals display a phenotype similar to previously reported Ltbp1L knockout mice. We reinvestigated the other "complete" knockout line and found that these mice express a splice variant of LTBP-1L and, therefore, are not complete Ltbp1 knockouts. Our results clarify the phenotypes of Ltbp1 null mice and re-emphasize the importance of LTBP-1 in vivo.

Keywords: Conditional knockout mice; Latent TGF-β binding protein; Persistent truncus arteriosus; Transforming growth factor β.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Exons
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Genes, Lethal*
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / pathology
  • Heart Defects, Congenital / veterinary*
  • Latent TGF-beta Binding Proteins / genetics*
  • Latent TGF-beta Binding Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism


  • Latent TGF-beta Binding Proteins
  • Ltbp1 protein, mouse
  • Protein Isoforms
  • Transforming Growth Factor beta