Abnormal adherence junctions in the heart and reduced angiogenesis in transgenic mice overexpressing mutant type XIII collagen.
Type XIII collagen is a type II transmembrane protein found at sites of cell adhesion. Transgenic mouse lines were generated by microinjection of a DNA construct directing the synthesis of truncated alpha1(XIII) chains. Shortened alpha 1(XIII) chains were synthesized by fibroblasts from mutant mice, and the lack of intracellular accumulation in immunofluorescent staining of tissues suggested that the mutant molecules were expressed on the cell surface. Transgene expression led to fetal lethality in offspring from heterozygous mating with two distinct phenotypes. The early phenotype fetuses were aborted by day 10.5 of development due to a lack of fusion of the chorionic and allantoic membranes. The late phenotype fetuses were aborted by day 13.5 of development and displayed a weak heartbeat, defects of the adherence junctions in the heart with detachment of myofilaments and abnormal staining for the adherence junction component cadherin. Decreased microvessel formation was observed in certain regions of the fetus and the placenta. These results indicate that type XIII collagen has an important role in certain adhesive interactions that are necessary for normal development.
Sund
M
M
Collagen Research Unit, Biocenter Oulu, Department of Medical Biochemistry, University of Oulu, PL 5000, 90014 Oulu, Finland.
Ylönen
R
R
Tuomisto
A
A
Sormunen
R
R
Tahkola
J
J
Kvist
A P
AP
Kontusaari
S
S
Autio-Harmainen
H
H
Pihlajaniemi
T
T
D022005:Adherens Junctions / Q000648:ultrastructure*; D000818:Animals; D003094:Collagen / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000002:abnormalities / Q000098:blood supply; D006321:Heart / Q000196:embryology; D006330:Heart Defects, Congenital / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009206:Myocardium / Q000648:ultrastructure; D018919:Neovascularization, Physiologic; D010641:Phenotype; D010920:Placenta / Q000002:abnormalities / Q000098:blood supply; D012333:RNA, Messenger / Q000096:biosynthesis; D016019:Survival Analysis
D012333:RNA, Messenger; D003094:Collagen