Double knockout

Apo E/CXCR3 double knockout mice on a high-fat diet displayed reduced atherosclerotic lesions during early stages of atherogenesis. 

Combadiere C, Potteaux S, Gao JL, et al. Decreased atherosclerotic lesion formation in CX3CRl/apolipoprotein E double knockout mice. Circulation 2003 107(7) 1009-1016. 

Reik If you look at ligands and receptors in double knockouts, these actions of IGF1 and IGF2 can be separated they are additive. 

Stanewsky There is one aspect of the Cry double knockout behaviour that has always puzzled me. It never looked to me that it was just masking, because they seem to anticipate the LD transition. This would fit perfectly with your assumption that it is an hour-glass mechanism. 

Jchibler Bert Van der Horst did an experiment where he showed that he couldn t induce circadian rhythms in Crj double knockout mouse embryonic fibroblasts. This is not surprising because they probably need the same components than in the clock. My strong prediction would be that everything is flat in the periphery. 

Van Gelder A clarification. The restored transplant is a wild-t3rpe SCN into a cry double knockout. Is the Crj double-mutant SCN-lesioned ... 

Schibler Bert van der Horst, did you ever try to food entrain a Crj double knockout One suggestion has been that you wouldn t need negative factors if you could regulate the clock by redox. 

Hastings In the SCN of the Cry double-knockout mice, the PER2 protein is destabilized. There is no PER2 protein, even though there is mRNA. In Steve s knockouts, if you knockout some of the PERs then you destabilize the CRYs. There is a reciprocal co-stabihzation taking place in the SCN. 

Takahashi If you have a mouse that is clockless it is much more susceptible to disturbances. In clock mutants that are arrhythmic, if you are not careful the noise in the animal facility wiU actually drive a diurnal day-active activity pattern. We see this in Cry double knockouts too. They are arrhythmic, so they are highly susceptible to being disturbed. This leads to this diurnal activity pattern. 

Sassone-Corsi That s a good question, and we haven t done this. I would expect the effects to be from the SCN, but we need to do this experiment. I would love to see a SCN transplant in a Clock mutant mouse. But if what Bert van der Horst said in his paper (Bonnefont et al 2003, this volume) is true, that peripheral clocks are not working in Cry double knockouts where a normal SCN is introduced, this teUs me that all peripheral oscillators are not crucial for motor rhythmic activity. Could the SCN be the only thing responsible for aU the rhythmic activity I am not sure how much peripheral tissues are working in those Cry double knockouts. 

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