I am doing a study involving comparing known blood reducing chemicals and potential cholesterol reducing extracts.
I know that Mus musculus is one of the model organisms for mammalian development and I was wondering whether it is a good species for observing blood cholesterol concentration (particularly LDL-C) differences.
If not, in what mammalian species (apart from humans) would you suggest I use?
This is not my field of work, but you may get good insight as to whether mouse is a good model from the ob/ob mice, despite developing many aspects of the metabolic syndrome, leptin deficient (ob/ob) mice do not spontaneously develop atherosclerosis, suggesting perhaps a reduction in cholesterol secretion, despite overt obesity. This may suggest they are not a good model. However, there are many different mus musculus models available, some may be better than others. What about cell models for rapid screening and then translation to animal - this may be a way forward. I hope this is of some help, at least in directing your search further.
I would contact technical support at the Jackson lab to talk with someone regarding any available mouse models best suited for your experiments.
http://research.jax.org/mousegenetics/Resources-for-researchers.html
First use different dosages of your compound in male (!) C57BL/6 mice of 6-8 weeks of age on normal chow for 7-14 days, then fast them for 4-6 hours (not over night!) and check plasma total cholesterol and apoB-depleted cholesterol levels. Should suffice for a first evaluation as to whether your compound works. Most lipid-lowering drugs work in B6, some contradicting reports exist on statins. If you'd like to check in a more "human-like" model, then use either male NZW rabbits or CETP-Tg mice which in contrast to B6 mice do have LDL-C in their plasma due to CETP activity. In a next step, you may challange either NZW rabbits or CETP-Tg mice with a high-fat, 0.2% cholesterol-enriched diet for 4-8 weeks, at later time-points plasma cholesterol levels can become over-saturated and the potential effect of a lipid-lowering compound may not be visible any more. If need to check atherosclerosis development, f.i. use male apE KO mice or male NZW rabbits and feed them with a high-fat, 0.2% cholesterol-enriched diet for 4 and 8-12 weeks, in order to assess early and late atherosclerosis development. Best,
Golden-Syrian hamster is superior as mice lack cholesterol ester transfer protein (CETP) activity:
http://www.criver.com/about-us/news-events/featured-stories/2013/hamster-hypercholesterolemia-model-now-available
Hamster is a good idea though! If there was the same number of antibodies and other tools commercially available as it is for mice, I would definitively use hamsters.
Hej Jason, if you can tell whether your compound is expected to affect intestinal cholesterol absorption, or apoB-production/LDL secretion, or LDL uptake in liver, or bile acid metabolism, I may be able to give you further suggestions which mouse would be interesting, maybe also a specific KO mouse...
Mouse are HDL animals, so for study cholesterol lowering substances you better can look for a LDL animal, or use a transgenic or knockout mouse
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