Muscles In The Mice With Dmd example essay topic

Imagine being a parent and discovering that your child won't be able to walk by the age of 12 and won't live past the age of 20. This has become a reality for many parents as they find out that their child has a form of muscular dystrophy. This particular type of muscular dystrophy is referred to as Duchenne Muscular Dystrophy, which is a genetically inherited disorder that is the most common and severe of all muscular. It is found in 1 of every 3,500 males and is characterized by progressive muscle wasting.

It is caused by the lack of dystrophic, which is a protein found in the cell membrane of muscles. One early clinical sign of the disease is the child showing a late start in walking and sometimes they are referred to as a late bloomer. Usually when the child walks they have a waddling motion and sometimes they walk up on their toes. Usually, hypertrophy, or enlarging of the muscles, especially in the calves is noticed.

However, the hypertrophy is actually caused by adipose (fat) tissue, which replaces the muscle tissue. This may make the muscles larger, but it doesn't make them any more useful (Cummings, 213). Another clinical sign of DMD is small amounts of mental retardation or learning disabilities. Although this is not apparent until the child is older, it is a common pattern that is found in children with DMD. There have been many studies done to determine what exactly causes the mental retardation. Researchers did a study in the early 1990's and found that the protein dystrophic was not only found in the muscles but also in the brain's cortex, cerebellum and hippocampus (Wahl).

This has led researchers to believe that if the muscles were lacking the dystrophic to cause the muscle degeneration then the brain must also be lacking the dystrophic, which could lead to different learning disabilities that are sometimes found in an individual with DMD. Duchenne's Muscular Dystrophy is an X-linked recessive genetic disorder caused by a deficiency of the protein dystrophic, which is found in muscle cells. This X-linked disorder is usually only found in males. It has very rarely been found in females because they have two X chromosomes and the disease is recessive.

The reason only males get DMD is because the source of the disease is found on the X chromosome of heterozygous females (Cummings, 108). They pass it on to one half of their sons and to one half of their daughters who become carriers. The Punnett square on the left illustrates the previous sentence: Xc XX XXC Xy XY X XXc XXc Xxc XY XY In the possibility that the male with DMD reproduces, his sons would not be infected however is daughters would be 100% carriers of the disease. The Punnett square on the right illustrates this. Even though DMD is present from the initial stages of fetal development, physical signs are not present until 18 months to 4 years of age. In addition to the clinical signs mentioned above, a child with DMD is unable to climb or pull itself up from the floor.

Between the ages 3 and 7, a child with DMD may show signs of improvement, but that is due to natural growth and development. In school they start to fall behind in being able to keep up with their peers in physical activity. This sometimes leads to them being called clumsy or lazy. When the child is around 9 years, the disease starts to progress rapidly and by age 12, they can no longer walk on their own. In the late stages, a significant loss of muscle tissue is noticeable. There may also be an increase of the curvature of the spine.

When they are brought to the doctor, a series of tests are done to determine the problem. When a biopsy is done, the doctors find that the muscle tissue has hypertrophied with adipose tissue. Shortly after the cells have become full of adipose tissue they die. Unlike other tissues of the body, muscle and nerve tissues cannot reproduce. An individual is born with a specific amount of muscle and nerve cells. Once they die, they cannot be regenerated.

This is bad news for people with DMD and they usually die around the age of 20 due to the diaphragm or heart muscle degenerating. As mentioned before, the main cause of Duchenne Muscular Dystrophy is the lack of dystrophic. The dystrophic gene is the largest gene that has been found and is quite complex. It is responsible of maintaining the shape and structure of the muscle fiber. So far the scientists who have been studying this gene have found eight promoters, four of which code for the brain form of dystrophic and one that codes for the muscle form (Wahl). Frame-shift mutations occur when a nucleotide base is either inserted or deleted causing a shift in the open-reading frame of that gene.

In a healthy individual, 14,000 base pairs are translated into 3,685 amino acids to make the protein dystrophic. When one of the bases is inserted or deleted it changes the reading frame to code for another amino acid, which isn't what is needed. When dystrophic isn't produced, the muscles do not form properly. Without support, the muscles tear when contracted and eventually die.

In a study of gene mutations, J.T. Den Dunnen examined 194 patients with Duchenne Muscular Dystrophy and a milder form of the same disease called Becker's Muscular Dystrophy (BMD). In BMD, a base-pair mutation occurs where only one base pair is altered not causing a problem in the open-reading frame. Dunnen measured the number of insertions and deletions in the various cases. He found that deletions were much more common and more lethal than insertions. He also found that DMD altered the reading frame, while BMD did not. In DMD, 98 out of 115 had deletions while only 17 out of 115 had deletions in BMD.

In DMD, 12 out of 13 had insertions, while only 1 out of 13 had insertions in BMD (Cummings, 358). There are several ways to test for Duchenne Muscular Dystrophy. The first is a blood test, called the serum creatine kinase test, looking for an increased amount of creatine kinase. Normally there is only a small amount of creatine kinase in the bloodstream. All muscles produce creatine kinase and release small amounts, however when the muscle cells tear from contracting, the creatine kinase leaks into the bloodstream. There may be anywhere from 10 to 100 times the normal amount in the bloodstream in a person with DMD ("Duchenne").

The second test that could be done is an test. This involves putting a small needle in the skin and recording the pattern of electricity. When muscles contract, there is an electric current flowing through the tissue. In a person with DMD, the electricity pattern is abnormal ("Duchenne"). The third way to test for the disease is a muscle biopsy. In this process a piece of muscle is removed and examined under the microscope.

When the cells are seen as enlarged and filled with adipose tissue then the disease is prevalent. Or another sign is if the muscle cells are dead. Also, the dystrophic in the cell membrane is missing ("Duchenne"). The last way to test is direct DNA testing.

While the child is still in the womb it can be tested for the disease by doing an amniocentesis. In this procedure, fluid and fetal cells are taken out from the amniotic layer that surrounds the fetus. Then the cells are checked for a defect or genetic mutation in the DNA. This is usually done if the mother is thought to be a carrier of the disease ("Duchenne"). At this time, there are many research studies being done to try and find a cure for Duchenne Muscular Dystrophy. Unfortunately, a definite cure has not been found yet.

One study involved the use of an antibiotic called injected in mice. Dr. H. Lee Sweeny and his colleagues at the University of Pennsylvania worked with mice that had a genetic disorder known as a "misplaced stop codon" that shuts down the production of dystrophic ("Study"). This had the same effects in the mice that a small percentage of DMD patients have. When Sweeney and his colleagues injected the mice with, they started to make dystrophic again. Sweeney said that if this treatment worked for people, as it did for the mice, then it could be used for other genetic diseases such as cystic fibrosis.

While this study does seem promising, there are a couple of downsides to it. One is that this would only work for a small portion of DMD patients because most DMD cases are a result of nucleotide base deletions rather than a "misplaced stop codon". Also, Sweeny said that could cause hearing and kidney problems if used routinely ("Study"). In another study, researchers found that stem cells taken from muscles or bone marrow of healthy donor mice and transplanted into mice with DMD can help regenerate the muscles those mice. Louis Kunkel and Emanuel la Gus soni of the Children's Hospital in Boston injected a solution of stem cells from healthy donor mice into the bloodstreams of mice with DMD. A few weeks later, the researchers found that the injected cells completely regenerated the bone marrow of the mice with DMD.

They also found that the muscles of the mice with DMD had some of the injected cells in them and also that the muscle cells were now producing dystrophic. Kunkel said "it's amazing that the donor cells contributed enormously to rebuilding of the dystrophic-deficient muscles, that they did so by entering the muscles from the bloodstream". ("Stem"). Even though this sounds like a major breakthrough, there are some problems that still need to be worked out. One is that the muscles in the mice with DMD only produced a small percentage of dystrophic. A method for increasing the amount of the injected healthy cells that go to the muscle needs to be found.

Also, in this experiment, the mice DMD had their bone marrow destroyed by a process called irradiation. In this process, X-Rays are used to destroy the targeted tissue. So this treatment wouldn't be able to used until the muscles become damaged. Kunkel says that they need to find a way to identify damage signals that muscles send out when degeneration begins ("Stem").

These are just two of the many research projects that are aimed at trying to find a cure for DMD. Hopefully, in the near future, the technology present now will help in trying to find one. Even though there is no cure for Duchenne Muscular Dystrophy, there are places people with disease can go to get help. There are several Support Groups out there to help people with DMD.

The Muscular Dystrophy Association or MDA is probably the largest support group. They offer financial and emotional support as well as a vast information site for all of the different muscular. They fund research projects that are aimed at finding a cure for the diseases and they also publish their own bimonthly magazine called "Quest". They can be found on the Internet at web Another support group is the The Parent Project for Muscular Dystrophy Research. Like the MDA, they also support families with DMD and fund research projects.

In conclusion, Duchenne Muscular Dystrophy is a severe form of muscular dystrophy that causes progressive muscle degeneration. Its main cause is the lack of the protein dystrophy that is necessary for the muscles to function properly. It is tough for the victims and their families because there is no definite cure and they usually don't live past the age of 20. Hopefully in the future, technology will enable researchers to be able to find a cure that will be a 100 percent effective when used. Until that time comes, all DMD victims can do is wait and hope.

Bibliography

Cummings, Michael R. & William S. Klug. Concepts of Genetics 4th Ed. New York: Macmillan College Publishing Company, 1994"Duchenne Muscular Dystrophy", web October 25, 1999.
Stem Cells Join Pipeline in Fight Against DMD". web December, 1999.
Study Impacts Muscular Dystrophy". web July, 1999.
Wahl, Margaret "The Brain in Duchenne Muscular Dystrophy". web January, 1997.