Category Archives: Publications

Recent publications from the lab

Hot off the press

hot pressCartilage-Specific Ablation of XBP1 Signaling in Mouse Results in a Chondrodysplasia Characterised by Reduced Chondrocyte Proliferation and Delayed Cartilage Maturation and Mineralization

T.L. Cameron, I.L. Gresshoff, K.M. Bella, K.A. Piróg, L. Sampurno, C.L. Hartley, E.M. Sanford, R. Wilson, J. Ermann, R.P. Boot-Handford, L.H. Glimcher, M.D. Briggs, J.F. Bateman

Osteoarthritis Cartilage. 2015 Jan 16th

Our first publication for 2014

EJHG

“Genotype to phenotype correlations in cartilage oligomeric matrix protein (COMP) associated chondrodysplasias” published in European Journal of Human Genetics.

March 5th

Available here ejhg201430a with supplemental information here ejhg201430x1.

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The first mutations in COMP were identified in 1995 in patients with both PSACH and MED and subsequently there has been over 30 publications describing COMP mutations in at least 250 PSACH–MED patients.

However, despite these discoveries, a methodical analysis of the relationship between COMP mutations and phenotypes has not been undertaken. In particular, there has, to date, been little correlation between the type and location of a COMP mutation and the resulting phenotype of PSACH or MED.

To determine if genotype to phenotype correlations could be derived for COMP, we collated 300 COMP mutations, including 25 recently identified novel mutations. The results of this analysis demonstrate that mutations in specific residues and/or regions of the type III repeats of COMP are significantly associated with either PSACH or MED.

This newly derived genotype to phenotype correlation may aid in determining the prognosis of PSACH and MED, including the prediction of disease severity, and in the long term guide genetic counselling and contribute to the clinical management of patients with these diseases.

2013; the year in review

Whilst this is not quite the Queen’s ‘Christmas Speech’ or the ‘State of the Union’ we still had a very busy year

Queens Speech

2013 was our first full year at the IGM and may well prove to be a watershed; so here are 10 things that happened in the lab that even Her Majesty would be proud of :-

1. We’ve said hello to some new faces; Beth, Robert and Ella, but sadly bid farewell to Etta who has moved to an new position in Cardiff. Sarah has now finished her lab work in Manchester and is busy writing her Phd Thesis.

2. We also had our first IGM ‘project student’; Helen Mackie who wrote an excellent project report and overall she achieved an upper second class degree (2.i). So congratulations to Helen!

3. We have had several excellent manuscripts published this year (and several others are still under review) :-

  • Abnormal chondrocyte apoptosis in the cartilage growth plate is influenced by genetic background and deletion of CHOP in a targeted mouse model of pseudoachondroplasia in PLOS ONE.
  • Mild Myopathy Is Associated with COMP but Not MATN3 Mutations in Mouse Models of Genetic Skeletal Diseases. PLoS One. 2013 Nov 27;8(11):e82412.
  • A novel transgenic mouse model of growth plate dysplasia reveals that decreased chondrocyte proliferation due to chronic ER stress is a key factor in reduced bone growth. Dis Model Mech. 2013 Sep 12.
  • Armet/Manf and Creld2 are components of a specialized ER stress response provoked by inappropriate formation of disulphide bonds: implications for genetic skeletal diseases. Hum Mol Genet. 2013 Aug 23.
  • Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures. Biol Open. 2013 Aug 15;2(8):802-11.

4. In addition, we have revised two GeneReviews™ articles :-

  • Multiple Epiphyseal Dysplasia, Dominant. Here.
  • Pseudoachondroplasia. Here.

5. In April we heard that SYBIL (Systems Biology for the Functional Validation of Genetic Determinants of Skeletal Diseases) had been favourably evaluated by the Commission services  and we proceeded to negotiations. SYBIL started in October.

6. We have had platform and/or poster presentations at the following Conferences or Workshops:-

  • ESCEO13-IOF Congress in Rome, Italy, April 17-20.
  • VI International Congress on Stress Proteins in Biology and Medicine in Sheffield, UK, August 18-22.
  • ISDS 11th Biennial Meeting in Bologna, Italy, August 28-31.
  • BSMB in Cardiff, UK, September 2-3.
  • “Lessons from Rare Diseases of Cartilage” in Liverpool, UK, October 16.
  • Pan Pacific Connective Tissue Societies Symposium in Hong Kong, China, November 24-27.

7. Pete was awarded a FEBS Fellowship in May to travel to Cologne and work with our good friends and colleagues  Frank and Raimund (below) on COMP and Tenascin interactions.

Cologne

8. Thanks to Beth, Rob, Kasia and Pete the lab is now fully ‘up and running’ and we have received all of our genetic models from Manchester and re-established necessary technology and resources in IGM @Newcastle. It’s taken about 12 months in total, but we are there now!

9. Kasia organised and hosted a Newcastle_Manchester Research day that was a great success and we plan for an even bigger event with Cologne in 2014 (watch this space!).

10. Pete was awarded an ISMB travel bursary to present at the Pan Pacific Connective Tissue Societies Symposium in Hong Kong, China, November 24-27 (and therefore advertise the blog!).Pete Hong Kong

11.…………we celebrated all these achievements accordingly!

Champagne