I am planing to use tamoxifen in mice to promote Cre excision of a floxed stop signal. I have read some publications where the authors wrote that they checked the mice for potential side effects. Could anyone tell me about those side effect? Are they frequent? (I am planing to inject 2mg tamoxifen/mouse daily during 5 days)
Studies done in mice have shown tamoxifen to mimic the effects of estrogen on bone metabolism and skeletal growth, which could possibly result in increased the possibility of pre-mature bone fusion. However, this effect would be less of a concern in adults who have stopped growing and in knock out mice where tamoxifen should be used only for a shorter period of time.
As I remember tamoxifen treatment could lead to development of liver tumors insome mouse strains. You can easily o find the references via PubMed
I did some Tamoxifen injection (5 IP daily with 1 mg/mice) in Vil-Cre_ERT2 mice.
I noticed during the necropsy, 8 weeks after, that 8 (over 18) mice display some blood in the stomach and for some in the small intestine. I thinks the bleeding was coming form the stomach.
The most important here was that both genoptype (Vil-Cre + or -) were affected, meaning that the injuries were potentially induced by tamoxifen itself.
And they were long-lasting as oppose to the Gastroenteology paper attached.
And since my Vil-Cre-ERT2 -/- mice were affected too (I did twice the genotyping to be sure), it is not due to Cre-driven injury (see the 2nd paper attached).
Hope it helps !
Article Inducible activation of Cre recombinase in adult mice causes...
Article Tamoxifen Induces Rapid, Reversible Atrophy, and Metaplasia ...
As I reember, it was reported that long-term treatment with tamoxifen induced liver tumors in mice
Tamoxifen will also cause dystocia in pregnant females. This is a problem when looking at knockouts in fetuses that are then allowed to birth. I have limited success with having these animals goive birth.
When I treat my cre-ERT2 mice with tamoxifen (2mg/mice) thrice intra-peritonially. Between 1-4week, I observe 5-6 mice (put of 60) die due to ataxia. Are there any suggestion as to whether this happens due to incorrect IP injections or just the effect of tamoxifen?
Tamoxifen treatments have been widely reported to produce toxicity or death in mice. This can include stomach, intestinal and liver cellular abnormalities. We ip inject tamoxifen at 2 mg/25 g mouse (C57BL/6J) in sunflower oil (suspended at 20 mg/ml by bath sonication at 37-55C) -- either daily x 5 days or every other day x 3-5 doses. The daily regimen has produced significant mortality on occasion. Both regimens have been shown to cause robust target gene deletion in CNS neurons or oligodendrocytes (with proper Cre promoters).
As I remember there is data on hepatoma development in tamoxifen-treated rodents