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 cel l adhesion. Transgenic mouse lines were generated by microinjection of a DN A construct directing the synthesis of truncated (alpha1(XIII) chains. Shor tened alpha1(XIII) chains were synthesized by fibroblasts from mutant mice, and the lack of intracellular accumulation in immunofluorescent staining o f tissues suggested that the mutant molecules were expressed on the cell su rface. Transgene expression led to fetal lethality in offspring from hetero zygous mating with two distinct phenotypes. The early phenotype fetuses wer e aborted by day 10.5 of development due to a lack of fusion of the chorion ic and allantoic membranes. The late phenotype fetuses were aborted by day 13.5 of development and displayed a weak heartbeat, defects of the adherenc e junctions in the heart with detachment of myofilaments and abnormal stain ing for the adherence junction component cadherin. Decreased microvessel fo rmation was observed in certain regions of the fetus and the placenta. Thes e results indicate that type XIII collagen has an important role in certain adhesive interactions that are necessary for normal development.