Hello everyone,
I wondered why NOD-Scid mice are suffering of irradiation exposure and nude mice not? I performed half brain irradiation in NOD-Scid model and after 5 days, all mice started to present bad clinical signs (piloerection, prostration, stop feeding and drinking,...) and I was obliged to sacrificed them because of their clinical state. Beside, I learned that nude mice are more appropriated for irradiation purpose. Do you know the reason? Do you have experience in this field? Does the immunologic background of NOD-Scid influence the management of the inflammation induced by irradiation?
Thanks a lot in advance for you comments !
2 potential factors - if my understanding is that you maintained the same radiation exposure in both NOD-Scid and nude mice. It may be related to the mutation on Chromosome 16 (in the NOD-Scid) affecting the activity of the enzyme involved in DNA repair (critical with radiation exposure) - and hence their innate sensitivity to irradiation. While nude mice have a chromosome 11 mutation rather than Chr 16. Also a potential factor is the combined T- & B-cell deficiency in the NOD-Scid while the nude nude mice are known to have leakiness (not apparent with NOD-Scid) and may actually produce some functional B & T cells although this is usually increases with age and it appears you sacrificed young?
Thanks a lot for your answer.
Yes I maintained both mice strains during the same period of exposure to irradiation.
They were sacrificed around 8 weeks old.
Do you know which enzyme is lacking in NOD-scid mice ? Maybe the DNA-PK ? Considering this I can understand that they cannot counteract DNA damage as they do not present the tools for this purpose...
Yes in humans it is the DNA-PK which functions with the Ku70/Ku80 heterodimer protein in DNA double stand break repair and recombination. I think the protein encoded is the P13/P14-kinase family [human]. Prkdc is in mouse which does not allow the VDJ recombination to occur resulting in immune and humoral maturation failure. http://www.ncbi.nlm.nih.gov/pubmed/3135329 reference just in case my mouse genetics is rusty.
My pleasure! This could have some interesting ramifications on a cellular level for humans answering the question why some people can tolerate high level radiation exposure with less adverse outcomes while others basically do what your NOD-scid mouse did....Fukushima survivors would be perfect candidates to answer these questions if we could get DNA samples.
Yes for sure! Its a really good question. The epigenetic/genetic and immunologic state of each person conditions the answer to radiation exposure...
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