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.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-6557-2 |
| Date | 13 November 2001 |
| Creators | Sund, M. (Malin) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2001 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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