PMID- 10331975
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20220414
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 126
IP  - 12
DP  - 1999 Jun
TI  - The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and
      positioning of the heart.
PG  - 2631-42
AB  - 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.
FAU - Clark, T G
AU  - Clark TG
AD  - Department of Pathology and Laboratory Medicine and Cardiovascular Research
      Center, University of Wisconsin, Madison, WI 53706, USA.
FAU - Conway, S J
AU  - Conway SJ
FAU - Scott, I C
AU  - Scott IC
FAU - Labosky, P A
AU  - Labosky PA
FAU - Winnier, G
AU  - Winnier G
FAU - Bundy, J
AU  - Bundy J
FAU - Hogan, B L
AU  - Hogan BL
FAU - Greenspan, D S
AU  - Greenspan DS
LA  - eng
GR  - AR43621/AR/NIAMS NIH HHS/United States
GR  - HL60104/HL/NHLBI NIH HHS/United States
GR  - HL60714/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Proteins)
RN  - EC 3.4.- (Metalloproteases)
RN  - EC 3.4.- (Tolloid-Like Metalloproteinases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.- (Tll1 protein, mouse)
RN  - EC 3.4.24.19 (Bmp1 protein, mouse)
RN  - EC 3.4.24.19 (Bone Morphogenetic Protein 1)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Protein 1
MH  - *Bone Morphogenetic Proteins
MH  - Female
MH  - Fetal Death/genetics
MH  - Gene Expression Regulation, Developmental
MH  - Heart/*embryology
MH  - Heart Defects, Congenital/*genetics
MH  - Heart Septal Defects, Atrial/genetics
MH  - Heart Septal Defects, Ventricular/genetics
MH  - Heart Ventricles/abnormalities
MH  - Homozygote
MH  - Male
MH  - Metalloendopeptidases/genetics/metabolism
MH  - Metalloproteases
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Myocardium/metabolism
MH  - Phenotype
MH  - Proteins/*genetics/metabolism
MH  - Recombination, Genetic
MH  - Tolloid-Like Metalloproteinases
EDAT- 1999/05/20 00:00
MHDA- 1999/05/20 00:01
CRDT- 1999/05/20 00:00
PHST- 1999/05/20 00:00 [pubmed]
PHST- 1999/05/20 00:01 [medline]
PHST- 1999/05/20 00:00 [entrez]
AID - 10.1242/dev.126.12.2631 [doi]
PST - ppublish
SO  - Development. 1999 Jun;126(12):2631-42. doi: 10.1242/dev.126.12.2631.