Tag: Mice

Mice Research Offers Possible Approach to Stopping Huntington's Disease

Researchers at the University of Iowa in Iowa City this month made public the results of their research into stopping dominant progressives brain disorders in mice.

A dominant progressive brain disorder is a disease caused when an infant inherits one copy of a mutant gene which results in the production of mutant proteins that cause loss of cognitive abilities. The most widely occurring form of this sort of disease in the United States is Huntington’s disease, with as many as 250,000 sufferers in this country alone. Huntington’s disease usually manifests itself in a victim’s mid-to-late 30s and sufferers typically live only 15-20 years after diagnosis while suffering progressively worsening brain degeneration.

The University of Iowa researchers used gene therapy to treat mice afflicted spioncerebellar ataxia type 1. The disease produces a mutated protein in the brain that eventually leads the mice to have difficulty in walking. Like Huntington’s it is not a result of a missing gene — which gene therapy has traditionally been used to treat in animal models and in a small number of humans — but rather a mutant gene inherited from a parent.

Nonetheless, researchers used a virus to carry modified genetic material to the mice. The genetic material was designed to bind with and block the expression the defective gene. After the mice were injected with the virus, the production of the proteins causing the disease stopped and the mice appeared to improve their ability to walk.

The researchers then took the process one step further and used the same method to see if genetic material could be effective when added in vitro to human Huntington’s cell cultures. After exposing the cell cultures to a different virus containing the genetic materials, the cells stopped producing the proteins that cause Huntington’s disease.

Lead researcher Beverley Davidson said the she hopes this discovery moves quickly into clinical trials to see if it can be effective in treating Huntington’s in human beings,

The data are very promising; we hope we will be able to use RNA interference as a therapy for dominant neurodegenerative diseases.

Source:

Cure hoped for Huntington’s sufferers. Erika Chek, Nature, June 9, 2004.

Eliminating Enzyme Suppresses Alzheimer's Symptoms in Mouse Model

Researchers at the Gladstone Institute of Neurological Disease recently published their research showing that removing a protein-regulating enzyme from mice suppressed Alzheimer’s symptoms in an animal model of the disease.

The researchers created genetically modified mice that expressed different levels of an enzyme known as Fyn. Fyn regulates the activities of many proteins. With Alzheimer’s disease, amyloid proteins accumulate in the brain and destroy synapses. In mice genetically engineered to completely block Fyn, however, the amyloid proteins were unable to damage the synapses and the mice lived much longer than typical mice used in the Alzheimer’s disease model.

Lead researcher Jeannie Chin said of the findings,

Our results suggest that Fyn lays a key role in Alzheimer’s-related synaptic impairments, and that it can worsen the toxicity of amyloid proteins. We are excited about the possibility that pharmacological modulation of Fyn might be of therapeutic benefit in this disease.

As Fyn plays a key role in a number of neurological processes, it is unlikely that it could be completely suppressed in human beings without severe side effects. The researchers plan to conduct further research to quantify what sort of benefit, if any, mice in the Alzheimer’s model receive from partial suppression of the enzyme.

Source:

Alzheimer’s pathology reduces, longevity improved in mouse model, Gladstone study shows. Press Release, University of California – San Francisco, May 19, 2004.

Researchers Find Gene that Causes Liver Cancer in Mice

Researchers at the University of Illinois at Chicago have discovered a gene that causes liver cancer in mice.

The gene, Foxm1b, plays an important role in allowing tissues to repair themselves in both mice and human being, but for some reason the gene is deactivated in humans as they age.

Dr. Robert Costa created a genetically modified mouse which had the Foxm1b gene deleted from the animals’ liver cells. The modified mouse did not develop liver cancer tumors and, in fact, Costa discovered he was unable to induce liver cancer tumors using a standard laboratory technique to do so. Without the Foxm1b gene, the mice appeared incapable of developing liver cancer.

In a press release announcing the publication of his findings in Genes and Development, Costa said,

To my knowledge, this is the first time a gene has been directly linked to the growth of cancer cells in live animals.

. . .

Foxm1b is expressed in many different kinds of cancer cells which leads us to believe it plays a key role in promoting the growth of tumors other than liver cancer.

Costa and his team of researchers also developed a prototype compound that inhibits Foxm1b and reduced the growth of cancer cell colonies in a laboratory setting.

Costa said,

We’re extremely excited about this finding because it suggests we might have a therapy for stemming the spread of liver cancer.

Source:

UIC researchers discover gene that causes liver cancer in animals. Press Release, University of Illinois at Chicago, April 1, 2004.

Mice or Cerebral Palsy Children: You Decide

Most people are aware that botulinum toxin (botox) is increasingly used for cosmetic purposes around the world. This has led to some protests by animal rights group because every batch of botox is tested on mice using an LD50 test to determine its potency. Because botulinum toxin is potentially deadly to human beings and each batch is of different toxicity, the LD50 test with mice is the only way to ensure that human beings receive a safe dose of botox.

Botox has a number of clinical uses beyond simply cosmetic, however. It is being used, for example, to treat muscle spasticity in the arms and hands of children with cerebral palsy.

In people with cerebral palsy, the brain sends abnormal messages to the muscles in the arms and legs which causes them to become too tense (spastic). This inhibits movement and makes it difficult for affected individuals to do common activities such as getting dressed or brushing teeth.

Since 1998, Wake Forest University research L. Andrew Koman has used botox to treat muscle spasticity. He recently reported on a study in which he injected 73 cerebral palsy patients with either botox or a placebo. Patients receiving the botox injection showed a three fold improvement in functional ability compared to those who received the placebo. The botox injections cause the muscles to relax, improving the ability of those with the disease to dress themselves and accomplish other tasks.

Interestingly, according to a Wake Forest University press release on using botox as a treatment,

Results vary from patient to patient depending on the severity of the disease. In addition, many of the children need fewer shots over time, are able to lengthen the time between injections, and even stop the injections completely, Koman said.

“Many of our patients come back into the office asking for additional injections because they are thrilled with the results,” he said. “Once the muscles have relaxed, patients can undergo therapy to strengthen weak muscles. Botox injections work very well in conjunction with other treatments.”

Of course there will always remain animal rights activists like Bill Maher or Ingrid Newkirk who will maintain that killing a few mice to allow children with cerebral palsy to improve their daily functioning is just not a tradeoff worth making.

Source:

Researchers at Wake Forest University Baptist use botox to treat CP. Press Release, Wake Forest University Baptist Medical Center, May 1, 2004.

Researchers Discover Genes Linked to Alzheimer's

Researchers at the Oregon Health & Science University recently announced they had identified a set of genes that are believed to play a role in the early development of Alzheimer’s disease.

In a press release announcing a forthcoming paper to be published in Human Molecular Genetics, lead researcher P. Hemachandra Reddy of the OHSU Neurological Sciences Institute said,

Through studying a mouse model of Alzheimer’s, the research team found that a series of genes related to mitochondrial metabolism in brain cells were more active than in normal mice. Mitochondria are structures located in the cytoplasm of cells that produce energy for the cell. Prior research has linked Alzheimer’s to mitochondrial function. However this is the first time genes that are responsible for early cellular change in Alzheimer’s disease pathogenesis have been identified.

. . .

We studied gene expression levels at three distinct stages of disease progression in the genetically-altered mice relative to age-matched wild-type normal mice. We conducted gene expression analysis long before (2 months of age), immediately before (5 months) and after (18 months) the appearance of beta amyloid plaques. In doing this, we found that these mitochondrial genes were more active at 2 months of age when compared to normal mice, and in some cases their activity heightened as the disease progressed. We believe the abnormal gene expression comes in response to beta amyloid-induced mitochondrial dysfunction, even in its early stages. Based on prior research, it’s thought that energy metabolism in mitochondria is impaired by heightened levels of beta amyloid in the brain. We believe the genes identified in our study increase their activity to compensate for this damage, but unfortunately in the end they cannot keep up with the progression of Alzheimer’s.

A companion study published in NeuroMolecular Medicine finds similar gene expressions in human Alzheimer’s patients, demonstrating the value of using a mouse model to study Alzheimer’s and, using this new finding, hopefully one day developing a test to detect the onset of Alzheimer’s early in the disease’s development.

Source:

OHSU researchers uncover genes involved in early stages of Alzheimer’s disease. Press Release, Oregon Health & Science University, April 27, 2004.

Researchers to Send Mice Into Space to Simulate Mars' Partial Gravity

The Telegraph reported in February on a joint British-American effort to send mice into orbit for an extended period of time in order to better understand the effects of living in a partial gravity environment.

The experiment, projected to cost 13 million pounds, would launch 15 mice into a near-Earth orbit for five weeks. The cylindrical spacecraft will spin in order to create a gravity effect similar to Mars. The spacecraft will then return to Earth and the mice studied for the effects that living in such an environment has on mammalian bodies.

Despite decades of space exploration, there is surprisingly little information on the effects of long-term exposure to living in such environments. The deleterious effects of long-term weightlessness are well documented thanks to the astronauts who live aboard the International Space Station. But according to Massachusetts Institute of Technology professor Paul Wooster,

The only data we have for partial gravity comes from the Apollo astronauts who spent a couple of days on the surface of the moon. . . Scientists do not yet know whether partial gravity is sufficient to prevent these health hazards [associated with living in a zero gravity environment]. A crew of mice will provide the first answer.

Maybe we could send a PETA activist along to protest and hand out “mouse astronaut” cards to any extraterrestrial children they might encounter.

Source:

‘Mouse-tronauts’ to pave way for men on Mars. Roger Highfield, Telegraph (UK), February 7, 2004.