Modelling Stickler Syndrome in Zebrafish
: An Investigation Into How Type XI Collagen Loss Leads To Premature Osteoarthritis Onset

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


Osteoarthritis (OA) is the most prevalent joint disease in the world, with nearly 9 million people estimated to be affected in the UK. During OA, articular cartilage at the joints is degraded to expose the underlying bone causing joint remodelling, pain and loss of joint function. OA is a multifactorial disease with genetics identified as a major risk factor. Previous work has estimated that up to 65% of all OA cases have a genetic contribution, with some of the most severe and premature forms of OA seen in humans with mutations in the collagen genes. An example of this is seen in Stickler syndrome, a hereditary group of conditions characterised by severe vitreal and musculoskeletal defects. In Type III Stickler syndrome, caused by mutations in the COL11A2 gene which encodes Type XI collagen, 75% of patients exhibit severe OA by the age of thirty; nearly 20 years earlier than OA becomes detectable amongst the general population. Previously, loss of Type XI collagen in mice and zebrafish has been shown to affect extracellular (ECM) composition, increase cartilage degradation and promote OA onset. However, the effect of Type XI collagen loss on the musculoskeletal system through development and into adulthood is yet to be understood.

In this thesis, I provide the first characterisation of the col11a2sa18324 zebrafish line to show significant changes to craniofacial cartilage morphology and ECM composition in larval stages, leading to a Stickler syndrome-like phenotype in adulthood. I show that col11a2sa18324 zebrafish experience altered strain distribution across the lower jaw cartilages, and that in wild type fish exposed to comparable strain abnormalities subtle changes to ECM composition and structure are seen. Finally, I demonstrate that major changes to the musculoskeletal phenotype in col11a2sa18324 fish coincides with the onset of behavioural changes which appear to be independent of pain.
Date of Award24 Jun 2021
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorHarry H Mellor (Supervisor) & Chrissy L Hammond (Supervisor)


  • Zebrafish
  • osteoarthritis
  • Stickler syndrome
  • collagen
  • hypergravity
  • behaviour
  • pain

Cite this