I've got some APP/PS1dE9 Alzheimer's disease Tg mice on a C57B/L6 background, which is not recommended on the Jax website because of increased mortality rates and seizures.
The original strain from Jax was on a mixed background with C57BL/6J and H3C but my strain has been bred with C57BL/6J wt. I'm not sure how serious this can get, does anyone have experience with this strain? Any suggestions would be greatly appreciated.
thanks in advance. Lin
http://jaxmice.jax.org/strain/004462.html
Lin, we are struggling with a similar problem but in the reverse direction: many of our biAT mice die early by epileptic problems in the original FVB background (Terwel et al, 2008) which appears to be rescued (or delayed) in the C57Bl6 background ...
work is in progress to get an handle on the issue !
Do you know what's the generation of your mouse? N9 or more than N13 (if you don't know, it will be difficult to decide whether it's worth to use the mouse as a good model), this should be important to your study. As the description of Jax website, the relationship between phenotype and genetic background is not quite consistent in different generation, you may have to figure out the seizure and mortality rate of your mouse first and try to compare that in different genetic back ground, but it takes time. You have to know the origin of your mouse and make sure they are. This make you to decide whether it's suitable for your study or you may have to give them up and buy a new one from Jax.
Just an experience with these mice. We had two adult TG males of 13 month and two WT females from the same colony of about 7 months. All were kept in the separate cages. One TG male arrived with 38 g weight, the weight of a mouse I have never seen, but was apparently healthy otherwise, behaved normally, no pain signs etc. No animal had any seizures whatsoever. Yet the mentioned male died within two weeks of arrival to our animal house, without being treated just before. We did some PET experiments with about 3 hours of isoflurane anesthesia about 5 days before. We have good keeping conditions of the animals and the sudden death rarely happens. The second TG male was about 28 g and keeps the weight. The animals strain is: B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, so the same which Lin have.
APP-induced premature death is quite high (50% or more depending on the location) with APP transgenes on B6, DBA/2J, FVB and other strains (Carlson et al., Hum Mol Gen 1997, 6:1951 and Krezowski et al. ,Hum Mol Genet 2004, 13:1989). This is not due to Aß peptides so I don't think the PS1 mutant exacerbates this.
You'll need to decide whether the inbred background is important enough to put up with having to breed more mice.
I have used several different amyloid tg mouse models (e.g. BRI-Abeta42, Tg2576, TgCRND8, APP/PS1-21, APP KI, and APP/PS1dE9) for more than 10 years. Based on my experience, APP/PS1dE9 mouse model on B6/C3 background does have a premature death phenotype but not as high as other APP tg mice. I know a few colleagues who tried to use APP/PS1dE9 mice on the pure B6 background for behavior testings but had to switch back to B6/C3 background due to the poor breeding performance (and apparently higher mortality). We are still sticking with B6/C3. Please note that this mouse model (like many other APP tg mouse models) has big sex differences in phenotypes. Example: http://www.ncbi.nlm.nih.gov/pubmed/20005821
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