Cloning And Characterisation Of A Novel Developmental Gene Involved In Myelination.
Funder
National Health and Medical Research Council
Funding Amount
$150,880.00
Summary
This project aims to identify and characterise a novel human gene involved in the formation of different organs and tissues, with an essential role in nervous system development. One of the most interesting facts of life, emerging from the completion of the Human Genome Project, is that it is not the number of genes but rather their regulation that plays the major role in evolution and determines the differences between species. The development of a human being from conception to birth is among ....This project aims to identify and characterise a novel human gene involved in the formation of different organs and tissues, with an essential role in nervous system development. One of the most interesting facts of life, emerging from the completion of the Human Genome Project, is that it is not the number of genes but rather their regulation that plays the major role in evolution and determines the differences between species. The development of a human being from conception to birth is among the most complex processes, where fine regulation of the timing and site of gene expression is crucial. We have recently identified a novel disorder where a mutation in a single gene disrupts the development and function of the eyes, the skull, the nervous, and the endocrine systems. The most disabling manifestations of the disease result from involvement of the peripheral nervous system. This is due to the failure of affected individuals to produce myelin, the insulating material that enwraps nerve fibres and facilitates the rapid conduction of nerve impulses. The mutated gene, which the project aims to identify, is likely to be involved in regulating the expression of multiple other genes essential for the early stages of myelination, as well as for the development of other tissues. The disease gene has been localised to a small interval on the long arm of chromosome 18, which does not contain any known developmental genes, suggesting that the project will provide novel information on the molecular pathways governing normal human development. As a result, the study may have important implications for understanding the general pathogenesis of disorders of the peripheral nervous system, including its common forms which affect thousand of people worldwide.Read moreRead less
After The Cloning Of The HMSNL Gene: Molecular Pathogenesis Of The Disease
Funder
National Health and Medical Research Council
Funding Amount
$258,564.00
Summary
We have completed an NHMRC-funded study, where we identified the gene for a severe disorder of the peripheral nervous system. The disease, hereditary motor and sensory neuropathy - Lom (HMSNL), presents with gait disturbances, difficulty in using the hands, muscle weakness and wasting and sensory loss. The concomitant impairment of the insulating myelin sheath surrounding nerve fibres (facilitating nerve conduction) and of the nerve fibres themselves suggests that the molecular defect lies in th ....We have completed an NHMRC-funded study, where we identified the gene for a severe disorder of the peripheral nervous system. The disease, hereditary motor and sensory neuropathy - Lom (HMSNL), presents with gait disturbances, difficulty in using the hands, muscle weakness and wasting and sensory loss. The concomitant impairment of the insulating myelin sheath surrounding nerve fibres (facilitating nerve conduction) and of the nerve fibres themselves suggests that the molecular defect lies in the basic mechanisms of interaction between the two main types of cell in the peripheral nervous system: the myelin-producing Schwann cell and the neuron. The two cells form the most complex system of communication in the human body, where signaling from one is vital for the development, functioning and survival of the other. Very little is known about the molecular mechanisms of this communication. At the same time, knowledge of the normal mechanisms of interaction is the key to better understanding of the mechanisms of disease in the peripheral nervous system and of the causes and possible prevention of the impairment of function. The newly identified HMSNL gene is probably involved in the signaling necessary for the development and functioning of the Schwann cell and for the survival of the nerve fibres. To gain an insight into the nature of the signaling cascade, we propose to use several complementary experimental approaches. We will create a mouse model of the human disease, to study its very early stages and subsequent evolution. In parallel, we will use molecular techniques and a yeast model, to identify other steps in the signaling cascade. The NHMRC-funded study will be part of a larger project conducted in collaboration with leading laboratories in the UK and the Netherlands, where other aspects of the molecular basis of the disease and of the role of the new gene will be examined.Read moreRead less