Tuesday, January 5, 2010

Accidental Discovery Advances Understanding of Spinal Cord Birth Defects

Accidental Discovery Advances Understanding of Spinal Cord Birth Defects

A report published in the December 6 issue of the journal Nature Cell Biology revealed a link between certain genetic mutations and early development of spinal cord disorders in mice. Scientists from the Johns Hopkins University School of Medicine and the University of California-Berkeley made the accidental discovery while searching for genes that guide the development and routing of the billions of neurons that make up the nervous systems of mice.

The study initially involved creating random mutations in mouse genes and then studying the offspring for nervous system defects. While examining thousands of mouse embryos as part of the study, graduate student Janna Merte noticed one of them had a spinal cord that had failed to develop from a flat sheet of cells into a tube.

Healthy spinal cord cells in mouse embryos develop at first in a flat layer of cells which then rolls up into a tube to begin forming the spinal cord. In spina bifida and other spinal cord disorders, the flat layer of cells never rolls up into a tube.

The mutated gene in the mouse embryo with the ill-developed spinal cord was identified by Merte as Sec24b, a gene already known to influence the process by which cells package proteins for the cell membrane or for delivery outside of the cell. The Johns Hopkins researchers then brought in Randy Schekman, the Berkeley professor who first discovered the Sec24 gene in yeast.

The team investigated another gene that, when mutated, led to similar problems with spinal cell tube closure in mice. The researchers discovered that the gene, known as Vangl2, was influenced by the presence of Sec24b. Further examination suggested that mutations in Sec24b and Vangl2 could be closely related to the development of spinal cord defects in humans.

Sixty-eight percent of mice engineered with mutations in both Sec24b and Vangl2 were born with spina bifida, which suggested to the scientists an integral interaction between the two genes.

Sec24b was found to be instrumental in spinal cord cells’ ability to properly package Vangl2. Mutations in either of the genes led to similar spinal cord defects in the animal models. The researchers’ discovery has opened the door to further studies in humans, which could lead to great advances in the understanding, prevention, and treatment of patients with spina bifida and other spinal cord disorders.


Johns Hopkins Medical Institutions. (December 28, 2009) “One Step Closer to Closure: Neuroscientists Discover Key to Spinal Cord Defects.” Retrieved December 29, 2009 from the Science Daily website: http://www.sciencedaily.com/releases/2009/12/091228090543.htm

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