Failure of ventral body wall closure in mouse embryos lacking a procollagen C-proteinase encoded by Bmp1, a mammalian gene related to Drosophila tolloid.
The mouse bone morphogenetic protein1 (Bmp1) gene encodes a secreted astacin metalloprotease that cleaves the COOH-propeptide of procollagen I, II and III. BMP-1 is also related to the product of the Drosophila patterning gene, tolloid (tld), which enhances the activity of the TGFbeta-related growth factor Decapentaplegic and promotes development of the dorsalmost amnioserosa. We have disrupted the mouse Bmp1 gene by deleting DNA sequences encoding the active site of the astacin-like protease domain common to all splice variants. Homozygous mutant embryos appear to have a normal skeleton, apart from reduced ossification of certain skull bones. However, they have a persistent herniation of the gut in the umbilical region and do not survive beyond birth. Analysis of the amnion of homozygous mutant embryos reveals the absence of the fold that normally tightly encloses the physiological hernia of the gut. At the electron microscopic level, the extracellular matrix of the amnion contains collagen fibrils with an abnormal morphology, consistent with the incorporation of partially processed procollagen molecules. Metabolical labelling and immunofluorescence studies also reveal abnormal processing and deposition of procollagen by homozygous mutant fibroblasts in culture.
Suzuki
N
N
Howard Hughes Medical Institute, Vanderbilt University Medical School, Nashville, TN 37232-2175, USA.
Labosky
P A
PA
Furuta
Y
Y
Hargett
L
L
Dunn
R
R
Fogo
A B
AB
Takahara
K
K
Peters
D M
DM
Greenspan
D S
DS
Hogan
B L
BL
D000650:Amnion / Q000196:embryology; D000818:Animals; D019521:Body Patterning; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000648:ultrastructure; D007422:Intestines / Q000196:embryology*; D008666:Metalloendopeptidases / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000196:embryology*; D016254:Mutagenesis, Insertional; D011347:Procollagen / Q000378:metabolism; D012886:Skull / Q000196:embryology; D014472:Umbilicus / Q000196:embryology
D019485:Bone Morphogenetic Proteins; D011347:Procollagen; D003094:Collagen; D008666:Metalloendopeptidases; C525707:Bmp1 protein, mouse; D055395:Bone Morphogenetic Protein 1