I've been looking for a mouse model for AD research, an inducible model would be most suitable for the original experiment design. I found a few Jackson tetO transgenic models, but there seems to be few researches with these models since their early descriptions in 2005 and only tet-off strains were generated despite the fact that both tet-off models by tetO x tTA and tet-on models by tetO x rtTA were said to be feasible on the Jax mice description page.
I was wondering why researches with inducible AD mouse modes are done and if there are further advancements in the models themselves after the descriptions a decade ago.
Are there any limits in generation of tet-on AD models?
little information available on the models makes me hesitate, since there are too many uncertainties. I'd really appreciate it if you can share your experience or knowledge with such models. Thanks.
Dear Lin Till now the pathological hallmark for Alzhimers disease is prenselinn gene, Beta amyloid and Tau protein. There is transgenic mouse for that one in Jax lab. So mostly people use this model for AD pathology studies. The model you are asking is less commonly used beacuse this are associate factor not a main cause of pathology
Pradip: Thanks for replying. The inducible mouse models I found actually express mutant APP, presenilin and tau, which are the same as those you mentioned. the difference here is that the expression of these genes are controlled by tetracycline in the inducible models I'm looking for, instead of spontaneous expression thoughout the entire lifespan, which better suits my initial experiment design.
I'm not sure about using such models 'cause I haven't got enough information on them and I think there might be aspects to these models preventing their prevalence that I don't know yet.
you can checkout the data sheet if you are interested.
http://jaxmice.jax.org/strain/015815.html
Dear Lin, depending on your experimental set-up, the Tet-system in the brain can sometimes cause some problems. If e.g. you want to keep the expression off during development and during early adult stages (= + Dox using the tTA system) and you want to induce it later, I have observed a strongly reduced expression pattern compared to the pattern you will get without Dox treatment (talking about the tTA based system). What works nicely is the opposite: expression during embryonic development until a certain timepoint, until the mice are treateed with Dox.
regards -
kai
Because it is not possible, while the so called Alyeimers diseases are very heterogenous entity of many cortical demantia syndromas. The diagnosis is postmortem, pathohystological. The speech, language and indirect memory deterioration are the dominant clinical signs of this syndromas.... Dr Aloise Alzheimer never spoke about "Alheimers disease"! He described only once patient with atypical pszchotic syndroma (Augusta D). How can you imitate this syndromas bz mouse??
dear Lin, the advice of Kai Schonig is most to the point.
First of all, define what you want to study and remember
/* AD is a complex disease of the brain, the most complex part of our body.
/* while amyloid & tau & inflammation are the post-mortem hallmarks (cfr Alzheimer himself) neither their origin & timeline & mutual relation during life before the dementia sets in are known
/* "inducible" implies that you have to treat the mice (pregnant mothers & foetuses & embryos !) with a drug, which interferes with normal physiological and abnormal pathological systems and mechanisms - far from ideal !
All mouse and other models have serious limitations in more than one aspect: number of human genes, number of mutations, integration ste effects, oveecpression evels, etc etc
No model is really 'good' - let alone ideal - but all help us somewhat to understand what AD is all about.
Nevertheless, the final answers are found only in the brain of the patient - cfr A. Alzheimer & Auguste D. (note her initials ...)
Excellent points--I agree totally with the flaws in the tau/plaques model--which has led medicine down a blind alley. I still say the solution for MOST cases of AD will go back to basic underlying causes relative to diet, hydration, heavy metal accumulations, food sensitivities, and hearing loss--once we frankly address these, leaving no stone unturned, we will see a marked decline of cases of AD and improvements in just about every case that is likewise addressed. It forever amazes me that the larger movement of medicine in the US ignored these as the culprits and instead focuses on the magic pill that does not and never will exist except to fatten the pocket books of medicine while it deceptively leads sufferers and their families down blind alleys.
thanks for all your replies! I've realized that there are flaws with these inducible models and there are too many uncertainties to be addressed.
I agree that animal models do not sufficiently recapitulate disease progression and there is no straight answer to the ideal model. However we have to choose one that suits the experiment design.
I've shifted my attention to commonly used transgenic mouse models for AD. I was wondering how reliable descriptions of these models can be, since there are variations in time of symptom onset and contradictions in cognitive impairments and I haven't got previous experience with transgenic mice.
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