Abrogation of both short and long forms of latent transforming growth factor-ß binding protein-1 causes defective cardiovascular development and is perinatally lethal.
Matrix Biol
; 43: 61-70, 2015 Apr.
Article
in En
| MEDLINE
| ID: mdl-25805620
ABSTRACT
Latent transforming growth factor-ß 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-ß (TGF-ß) 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Isoforms
/
Latent TGF-beta Binding Proteins
/
Genes, Lethal
/
Heart Defects, Congenital
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Matrix Biol
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2015
Document type:
Article
Affiliation country:
United States