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Oulun yliopiston väitöskirjat

THE ROLES OF COLLAGENS XV AND XVIII IN VESSEL FORMATION, THE FUNCTION OF RECOMBINANT HUMAN FULL-LENGTH TYPE XV COLLAGEN AND THE ROLES OF COLLAGEN XV AND LAMININ á4 IN PERIPHERAL NERVE DEVELOPMENT AND FUNCTION, ACTA UNIVERSITATIS OULUENSIS D Medica 1082

ISBN-13:	978-951-42-6365-1
Kieli:	englanti
Kustantaja:	Oulun yliopisto
Oppiaine:	Lääketiede,farmasia
Painosvuosi:	2010
Sidosasu:	pehmeäkantinen
Sijainti:	Print Tietotalo
Sivumäärä:	116
Tekijät:	HURSKAINEN MERJA

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Transgenic mice were used to evaluate the roles of collagens XV and XVIII in retinal vesseldevelopment and to examine the roles of collagen XV and laminin á4 in peripheral nervedevelopment and function. Also, in vitro methods were used to study the functions of recombinant,full-length human collagen XV produced in insect cells. The lack of collagen XVIII alone was found to result in overproliferation of astrocytes in themouse retina and deficient vascularization of the retina, which was ultimately rescued by thepersistent hyaloid vessels. VEGF mRNA expression was appropriately regulated in the retina ofthe collagen XVIII deficient mice, which also showed reduced susceptibility to oxygen-inducedneovascularization. Lack of collagen XV alone had no obvious effect on the mouse eye, but anabnormal migration of astrocytes onto the persistent hyaloid vessels could be seen in mice lackingboth collagens XVIII and XV. Recombinant full-length human collagen XV was seen in rotary shadowing EM as an extendedprotein with numerous kinks and a globular domain at its N-terminus. The mean length of themolecules was 241 nm and they had a tendency to form aggregates. Collagen XV attaches to thecollagen binding region of fibronectin and to a lesser extent to vitronectin and laminin. It wasrapidly bound to cultured cells with a staining pattern co-localizing with fibronectin. Collagen XVwas also found to inhibit the adhesion and migration of cells in vitro. Lack of collagen XV in mice was found to result in ultrastructural abnormalities in the sciaticnerves, such as polyaxonal myelination and more loosely packed C-fibres, mild impairment of BMassembly and mild motor dysfunction with a lower sensory nerve conduction velocity. Polyaxonalmyelination and a failure in the segregation of axons were evident in laminin á4 null mice, whichalso had diminished amounts of C-fibres, BM abnormalities, diminished myelin and a greatermyelin period compared with wild-type mice. They performed poorly in the round beam test andshowed diminished compound muscle action potentials. A simultaneous lack of collagen XV andlaminin á4 resulted in a permanent defect in the segregation of axons and C-fibre development.The performance of the double null mice on the round beam was poor relative to the othergenotypes.

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