Team creates LEDs, photovoltaic cells, and light detectors using novel one-molecule-thick material.
A major unsolved problem in medicine is the inability to regenerate nerve cells damaged by injury or disease. Efforts to understand the complex interactions that promote nerve cell growth and survival-focusing primarily on isolated nerve cells in culture-have produced limited and often conflicting results.
In the March 10 issue of Nature, scientists from the Whitehead Institute for Biomedical Research and MIT report a new approach to the problem.
Using new gene transfer technologies, they have created the first animal model completely lacking one of the four known neurotrophin molecules (a family of substances that promote survival and differentiation of various nerve cell populations). This model will greatly advance understanding of nerve cell development and also should be useful in evaluating potential treatments for human neurological diseases.
Dr. Patrik Ernfors, Dr. Kuo-Fen Lee, and Dr. Rudolf Jaenisch of the Whitehead Institute have developed a mouse strain with a specific mutation in the gene encoding brain-derived neurotrophic factor, or BDNF.
Previous studies by other researchers have shown that BDNF can prevent the deaths of certain populations of neurons in culture and rescue motor neurons in newborn laboratory animals. Based on this information, some scientists have proposed using recombinant human BDNF to treat motor neuron diseases such as amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's Disease).
"The new animal model will provide a system for assessing the potential success of such therapies," says Dr. Jaenisch, a member of the Whitehead Institute and professor of biology at MIT. "Already, it has shown us that some early assumptions about BDNF function may be incorrect."
For example, studies showing that BDNF could rescue motor neurons in newborn animals led to speculation that BDNF might influence motor neuron survival during development. However, the new BDNF mutant mice do not have any obvious defects in motor neuron development.
Dr. Ernfors and his colleagues suggest two possible explanations for these results. Either the earlier studies did not give an accurate reflection of the role of BDNF during development-new gene knock-out strategies offer a much more precise way of assessing gene function in the intact animal than traditional methods-or other neurotrophins in the mutant mice are compensating for the loss of BDNF.
Future studies of the new mouse strain will help scientists unravel this important puzzle. The ultimate goal is to understand how different neurotrophins interact during neural development to produce an intact embryo, and then learn to recreate those interactions to heal or rescue damaged nerve cells later in life.
The BDNF mutant mice do show specific defects in sensory neurons, the cells that transmit information from sensory organs such as the skin and tongue back to the brain. Perhaps the most dramatic example of this problem is the failure of the organ in the inner ear that controls balance. The mutant mice have severe balance problems because they do not have nerve cells capable of providing information to the brain about the position or state of motion of the head.
The Whitehead researchers developed this important new model for studying neurological disease using advanced transgenic technologies. Dr. Ernfors and his associates inserted a mutant BDNF gene into mouse cells in culture (embryonic stem cells) and then injected the altered cells into very early mouse embryos. Some of the resulting animals had the capacity to pass the mutant BDNF gene to their offspring; within two generations, the researchers had animals carrying two copies of the mutant gene in every cell.
This research was supported by the National Institutes of Health. In addition, Dr. Ernfors is supported by a fellowship from the Swedish Medical Research Council and Dr. Lee by a fellowship from Amgen, Inc. Dr. Ernfors is a postdoctoral fellow at the Whitehead Institute and Dr. Lee is a postdoctoral associate.
A version of this article appeared in the March 16, 1994 issue of MIT Tech Talk (Volume 38, Number 26).