Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart.

Publication ,  Journal Article
Clark, TG; Conway, SJ; Scott, IC; Labosky, PA; Winnier, G; Bundy, J; Hogan, BL; Greenspan, DS
Published in: Development
June 1999

Mammalian Tolloid-like 1 (mTLL-1) is an astacin-like metalloprotease, highly similar in domain structure to the morphogenetically important proteases bone morphogenetic protein-1 (BMP-1) and Drosophila Tolloid. To investigate possible roles for mTLL-1 in mammalian development, we have used gene targeting in ES cells to produce mice with a disrupted allele for the corresponding gene, Tll1. Homozygous mutants were embryonic lethal, with death at mid-gestation from cardiac failure and a unique constellation of developmental defects that were apparently confined solely to the heart. Constant features were incomplete formation of the muscular interventricular septum and an abnormal and novel positioning of the heart and aorta. Consistent with roles in cardiac development, Tll1 expression was specific to precardiac tissue and endocardium in 7.5 and 8.5 days p.c. embryos, respectively. Tll1 expression was also high in the developing interventricular septum, where expression of the BMP-1 gene, Bmp1, was not observed. Cardiac structures that were not affected in Tll1-/- embryos either showed no Tll1 expression (atrio-ventricular cushions) or showed overlapping expression of Tll1 and Bmp1 (aortico-pulmonary septum), suggesting that products of the Bmp1 gene may be capable of functionally substituting for mTLL-1 at sites in which they are co-expressed. Together, the various data show that mTLL-1 plays multiple roles in formation of the mammalian heart and is essential for formation of the interventricular septum.

Duke Scholars

Published In

Development

DOI

ISSN

0950-1991

Publication Date

June 1999

Volume

126

Issue

12

Start / End Page

2631 / 2642

Location

England

Related Subject Headings

  • Tolloid-Like Metalloproteinases
  • Recombination, Genetic
  • Proteins
  • Phenotype
  • Myocardium
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
  • Metalloproteases
  • Metalloendopeptidases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Clark, T. G., Conway, S. J., Scott, I. C., Labosky, P. A., Winnier, G., Bundy, J., … Greenspan, D. S. (1999). The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart. Development, 126(12), 2631–2642. https://doi.org/10.1242/dev.126.12.2631
Clark, T. G., S. J. Conway, I. C. Scott, P. A. Labosky, G. Winnier, J. Bundy, B. L. Hogan, and D. S. Greenspan. “The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart.Development 126, no. 12 (June 1999): 2631–42. https://doi.org/10.1242/dev.126.12.2631.
Clark TG, Conway SJ, Scott IC, Labosky PA, Winnier G, Bundy J, et al. The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart. Development. 1999 Jun;126(12):2631–42.
Clark, T. G., et al. “The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart.Development, vol. 126, no. 12, June 1999, pp. 2631–42. Pubmed, doi:10.1242/dev.126.12.2631.
Clark TG, Conway SJ, Scott IC, Labosky PA, Winnier G, Bundy J, Hogan BL, Greenspan DS. The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart. Development. 1999 Jun;126(12):2631–2642.
Journal cover image

Published In

Development

DOI

ISSN

0950-1991

Publication Date

June 1999

Volume

126

Issue

12

Start / End Page

2631 / 2642

Location

England

Related Subject Headings

  • Tolloid-Like Metalloproteinases
  • Recombination, Genetic
  • Proteins
  • Phenotype
  • Myocardium
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
  • Metalloproteases
  • Metalloendopeptidases