University of Oulu

Type XVIII and XV collagens: primary structure of human alpha1(XVIII) chain, phenotypic studies of type XVIII collagen single null and type XVIII and XV collagen double null mice

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Author: Ylikärppä, Ritva1,2,3
Organizations: 1University of Oulu, Collagen Research Unit
2University of Oulu, Biocenter Oulu
3University of Oulu, Faculty of Medicine, Department of Medical Biochemistry and Molecular Biology
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Version: published version
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Language: English
Published: 2003
Publish Date: 2003-10-24
Thesis type: Doctoral Dissertation
Defence Note: Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium L101 of the Department of Medical Biochemistry and Molecular Biology, on October 24th, 2003, at 1 p.m.
Reviewer: Ph.D., B.Sc. Raymond Boot-Handford
Professor Anders Kvanta


In this thesis study, the primary structure of the human α1(XVIII) polypeptide was elucidated, its tissue distribution was studied, and the phenotypic changes in the mouse eye due to lack of type XVIII collagen in a knock-out mouse model were studied further. In addition, the consequences of simultaneous lack of both type XVIII and XV collagen were studied in a mouse model lacking both of these proteins.

Two variant forms of human α1(XVIII) polypeptide were identified in this study, although, to date, a third form has also been characterized. The analysis of tissue distribution of the two polypeptide forms revealed differences in their tissue distribution, since the longest variant occurs prominently in the liver, while the short form is the major transcript in other tissues studied, e.g. in the kidney. The study of the type XVIII single null mouse eyes revealed abnormalities in the anterior eye segment in addition to the previously reported defects in the posterior eye part. In the type XVIII single null mice the iris was fragmented, pigment deposits could be seen in the pupil, and the pupillary ruff in the edge of a normal mouse iris was missing in these mice. The ciliary body was also abnormal, since the ciliary processes start to show regression in adult animals and eventually the basal infoldings of the non-pigmented ciliary body epithelia become flattened in the null mice. The intraocular pressure stabilizes to a lower level in adult mutant mice compared to controls, most likely reflecting the atrophied ciliary epithelia. The BM zones were also defective in the type XVIII null mouse eyes. The absence of an immunosignal with one of the antibodies detecting laminin γ2 chain in the type XVIII null mouse eyes may implicate conformational changes in the laminin γ2 chain due to lack of type XVIII collagen, and subsequently interaction between type XVIII collagen and laminin γ2 chain in normal mouse eye BMs. The study of the type XVIII and XV double null mice revealed that these mice were viable and fertile and had no major additional abnormalities compared to both single null mice. However, the regression of hyaloid capillaries (vasa hyaloidea propria, VHP) was studied in these mice, and a slight delay in the detachment of these vessels from the retina was noticed. Thus, the two collagens do not function entirely independently from each other.

The studies with type XVIII collagen single null mice indicate that in addition to the posterior eye phenotype, this collagen is needed for the normal structural integrity of the anterior eye segment and basement membranes of the eye. The mouse model lacking both type XVIII and type XV collagen indicates that the roles of the two collagens are essentially diverse, although a slight compensatory effect was observed in the detachment of the hyaloid capillaries from the retina.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 951-42-7141-6
ISBN Print: 951-42-7140-8
Issue: 753
Copyright information: © University of Oulu, 2003. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.