A zebrafish with a rare childhood bone disease.

Multiple osteochondromas.

One disease which our research has already shed light on is called multiple osteochondromas. This is a dominant genetic disease  which results in the formation of benign skeletal tumours in children. Besides causing severe skeletal deformity, the bone tumours can compress nerves or other tissue resulting in chronic pain. Although the tumours can often be removed by a surgeon, they sometimes recur or are in positions that prevent surgery. In some children, tumours form so frequently that they spend much of the youth preparing for and recovering from orthopaedic surgery. Once patients reach adulthood, the occurrence of new tumours stops. However, approximately 1 in 50 patients develop a type of cancer called chondrosarcoma. This is a far higher risk than is found in the normal population. This cancer, although slow growing, is potentially life threatening. Treatment sometimes involves limb amputation, radiotherapy  and/or chemotherapy.

A model for the development of osteochondromas

Our research:

We have identified strains of zebrafish that have skeletal defects which resemble those of patients with multiple osteochondromas. We have found that each strain carries a mutated form of an essential gene and this gene is also defective in patients with multiple osteochondromas.  Thus by analysing the function of this gene in the skeleton of zebrafish, we may shed light on how it works in humans. Zebrafish are small and the skeleton is very simple, this makes designing and performing experiments very easy. An important goal in our research is to identify all of the genes and molecules that are involved in the formation of bone tumours. This knowledge would provide targets for biochemists and pharmaceutical companies to design drug treatments.

Picture of normal (left) and ‘tumour’ cartilage (right)

The genetics of disease explained.

Inherited diseases are caused when mutations (stable changes in our DNA) occur that are carried from one generation to the next. The mutations affect the function of one or more genes that are required for our bodies to work properly.  When mutated to become defective, we refer to the altered form of the gene as a disease gene. Genetic diseases can be described as dominant or recessive. With recessive diseases, people can be carriers of the defective gene without even knowing it. The problem occurs when two carriers have children, then some of their offspring are likely to have the disease symptoms. Dominant diseases are those that affect all individuals with the defective gene, even if only one of their parents carries the disease gene. Most of these disease genes have a late onset (after adulthood), so affected individuals often have children before finding out that they carry the disease. With some dominant diseases, certain individuals have very mild symptoms, while other members of the same family will have severe symptoms (it is not known why this is). Thus even with dominant diseases, people may decide to have children without knowing that they carry the disease gene.

Further reading:

- Sugars, bones and a disease called Multiple Hereditary Exostoses.

- Regulation of zebrafish skeletogenesis by ext2/dackel and papst1/pinscher.

External links:

- The MHE Research Foundation (US)

- Hereditary Multiple Exostoses Support Group (UK)


Roehl Lab