Abstract

Type XIII collagen is a type II oriented transmembrane protein with a short intracellular domain, a single transmembrane domain and a large, mostly collagenous extracellular domain. Tissue localization and cell culture studies have implicated that it is involved in cell adhesion.

The spatio-temporal expression of type XIII collagen mRNA and protein during murine development is studied here. Type XIII collagen mRNAs were expressed at a constant rate during development, with an increase of expression towards birth. The strongest expression was detected in the central and peripheral nervous systems of the developing mouse fetus. Cultured primary neurons expressed this collagen, and recombinant type XIII collagen was found to enhance neurite outgrowth. Strong expression was also detected in the heart, with localization to cell-cell contacts and perinatal accentuation in the intercalated discs. Other sites of type XIII collagen expression included cartilage, bone, skeletal muscle, lung, intestine and skin. Clear developmental shifts in expression suggest a role in endochondral ossification of bone and the branching morphogenesis in the lung.

To elucidate the function of type XIII collagen transgenic mice were generated by microinjection of a cDNA construct that directs the synthesis of truncated α1(XIII) chains with an in-frame deletion of the central collagenous COL2 domain. This construct was thought to disrupt the assembly of normal type XIII collagen trimers. Expression of shortened α1(XIII) chains by fibroblasts derived from mutant mice was demonstrated, and the lack of intracellular accumulation in immunohistochemical analysis of tissues suggested that the mutant molecules were expressed on the cell surface. Transgene expression led to developmental arrest and fetal mortality in offspring from heterozygous mating with two distinct phenotypes. The early phenotype fetuses were aborted by day 10.5 of development due to a failure in the fusion of the chorion and allantois membranes and subsequent disruption in placentation, while the late phenotype fetuses were aborted by day 13.5 of development due to cardiovascular and placental defects. Furthermore, it was shown that the heterozygous mice that were initially of normal appearance and bred normally had an increased susceptibility to develop T-cell lymphomas and angiosarcomas later in life.

The results presented here increase the evidence that type XIII collagen is involved in cell adhesion, with several important tasks during development. A role of type XIII collagen in malignant transformation of certain mesenchymal cell populations is also implicated.