Model Organisms
When researching a human disease, it is beneficial to use model organisms to understand the disease and develop treatments. Model organisms are organisms that are easy to manipulate, have fast reproductive cycles, large brood sizes, and are cost and time efficient. Through the process of RNA intereference (RNAi), genes can be knocked out in these organisms. Knocking out these genes results in phenotypes similar to what would be seen in humans that have a mutation in their homologous gene. In researching SMPD1, I looked at the homologous genes in C.elegans (ASM-2), Drosophila (CG3376), and Mice (SMPD1).
SMPD1 Phenotypes in Model Organisms
Currently there is no phenotype information available for C.elegans by searching WormBase.
Using FlyBase phenotypes were found for the gene CG3376 in flies. Flies experience semi-lethality in the pupal stage, but are viable if they survive into the adult stage. This is similar to humans because people with Niemann-Pick Type A do not survive into adulthood, but if they have Niemann-Pick Type B they can survive into adulthood. Both of these types are caused by a mutation in the same gene. The flies were all found to be fertile, which is also consistent with humans because their fertility is not altered by this gene [1]. |
The mouse database MGI was used to identify phenotypes in mice. In the mouse, SMPD1 is located on chromosome 7. If mice are missing both alleles for SMPD1, they exhibit a variety of phenotypes, some of which are similar to those exhibited in humans. Similar phenotypes are tremors, ataxia, hepatosplenomegaly, and altered lipid homeostasis. Mice have also shown reduced weight, sperm defects, hunched posture, and abnormal cell death [2]. |
Analysis and Discussion
Since drosophila and mice were both found to have phenotypes similar to humans they would be good to use as model organisms when researching Niemann-Pick disease. Mice are more closely related to humans than flies and share more common phenotypes, so they would be the best choice to use out of the two. In fact, mouse models have previously been used in studies pertaining to human Niemann-Pick disease types A and B. In my Future Directions, I obtained information from the Drosophila protein interaction network, and want to test my hypotheses using mice because they are good model organisms.
References
[Fly Picture] retrieved from http://en.wikipedia.org/wiki/File:Drosophila_repleta_lateral.jpg
[Mouse Picture] retrieved from http://www.mus-musculus.com/
[1] http://flybase.org/reports/FBgn0034997.html
[2] http://www.informatics.jax.org/marker/MGI:98325
WormBase
FlyBase
MGI
[Fly Picture] retrieved from http://en.wikipedia.org/wiki/File:Drosophila_repleta_lateral.jpg
[Mouse Picture] retrieved from http://www.mus-musculus.com/
[1] http://flybase.org/reports/FBgn0034997.html
[2] http://www.informatics.jax.org/marker/MGI:98325
WormBase
FlyBase
MGI