Caltech Genetic Engineers Cure an Inherited Disorder in Mice
Scientists at Caltech, using genetic engineering techniques, have cured mice of an inherited neurological disease that causes them to shiver uncontrollably and die an early death.
The disease, called shiverer mutation, involves a deficiency of myelin basic protein, which accounts for about 30% of the insulating material that sheathes nerves in both humans and mice, just as plastic insulators enclose copper wires in electrical cords.
The mouse disease has no precise counterpart in humans, said biologist Leroy Hood, but there are at least 40 human disorders, such as multiple sclerosis, that involve defects in nerve sheathes.
The new work should lead to a much better understanding of how myelin basic protein is incorporated into nerve sheathes, he said, and may thus lead to a better understanding of these diseases.
The study “is of great interest,” said neurologist Scott Linthicum of the University of Texas Health Center, and “points the way to doing these things . . . for other diseases.”
A team led by Hood and Caltech biologist Carol Readhead reports the development in today’s issue of the journal Cell.
The shiverer mice appear normal at birth, but within 14 days their hindquarters begin shivering and they walk with an odd, rolling gait, Hood said in an interview. By the age of 1 month, they begin to have convulsions and, within three or four months, they die. Mice normally live two to three years.
Neurologist Richard Sidman of Harvard Medical School, who is part of the team, found that the gene for myelin basic protein resides on chromosome 18 of the mice. Hood’s group found that part of the gene was missing in the shiverer mice.
They then isolated the intact gene, complete with the DNA sequences that control its operation, from healthy mice and cloned it to produce multiple copies.
Using a long, thin needle, they then injected about 200 copies of the gene into each of 350 fertilized eggs from a female shiverer mouse.
The eggs were then implanted in females and grown to maturity. The genetic defect was corrected in one of the 350 offspring; the mouse did not shiver and had a normal life span.
Two more generations of mice have been produced from the cured mouse and they, too, are cured, indicating that the gene is incorporated into their DNA.
“The important thing about this experiment is that the inserted gene is expressed at the right time during development and in the right location--the brain,” Hood said.
The Caltech work is not the first time that genetic engineering has been used to cure an inherited defect.
In December, for example, scientists at Genentech Inc. of South San Francisco reported that they had cured mice of an inherited hormone deficiency that prevented normal sexual development and made the mice infertile.
