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Selected Publication:

Publication type: Doctoral Thesis

Year: 2018

Author(s): Beierfuß, Anja

Title: Untersuchung der Bandscheibendegeneration in Apolipoprotein E Knockout-Kaninchen.

Other title: Investigation of Intervertebral Disc Degeneration in Apolipoprotein E Knockout-Rabbits

Source: Dissertation, Vet. Med. Univ. Wien, pp. 35.


Advisor(s):

Rülicke Thomas

Reviewer(s):
Hennig-Pauka Isabel


Abstract:
Intervertebral disc degeneration (IVD), which catalyses the biological decomposition of intervertebral discs is valid as one of the most frequent causes for chronic back pains. Deficiency of apolipoprotein E (APOE) is one of the most important biological factors that trigger the development of arteriosclerosis. Arteriosclerotic plaques, which lead to the obstruction of the arterial supply to the lumbar spine, could cause intervertebral disc degeneration and subsequently chronic back pain. It was presented recently that APOE-knockout rabbits could show the symptoms of human arteriosclerosis along with hyperlipidemia and raised concentrations of cholesterol and triglycerides. We investigated for the first time IVD degeneration in lumbar spines of APOE-knockout rabbits, to clarify whether APOE-knockout rabbits are suited as a degeneration model for therapeutic attempts. For the investigation of ten homozygous APOE-knockout and four wild-type New Zealand White rabbits of the same age the methods of T1/T2-weighted magnet resonance tomography (MRI), glucose-oxidase test (GOD-Test), cell viability assay (MTT assay), real time quantitative PCR (RT-qPCR), western blot and enzyme-linked immunosorbent assay (ELISA) were applied. The results of the MRI analysis clearly showed a progressed intervertebral disc degeneration, obstructions of lumbar arteries and lower enrichments of contrast medium in IVDs of the APOE-knockout rabbits. In addition, IVDs of APOE-knockout rabbits showed lower concentrations of glucose and viable cells with altered concentrations of aggrecan, collagen II and collagen I (p < 0.0001). Deficiency of APOE in rabbits could induce an IVD degeneration that showed the symptoms of progressed IVD degeneration in humans. Currently an IVD degeneration is induced in animal models by surgical interventions. APOE-knockout rabbits, which make this surgical intervention redundant, can be utilised as a more appropriate animal model. Moreover, APOE-knockout rabbits could be used parallel for therapeutic attempts in degenerative IVD diseases and arteriosclerosis, and so contribute to the application of the "3R-principle".


Publication(s) resulting from University thesis:

Beierfuß, A; Dietrich, H; Kremser, C; Hunjadi, M; Ritsch, A; Rülicke, T; Thomé, C; Mern, DS (2017): Knockout of Apolipoprotein E in rabbit promotes premature intervertebral disc degeneration: A new in vivo model for therapeutic approaches of spinal disc disorders. PLoS One. 2017; 12(11):e0187564
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