Interestingly, the hallmark phenotype of all long-lived mouse models containing mutations that induce GH/IGF-1 deficiency or resistance, is their enhanced insulin sensitivity [ 6].
Following these proof of principle experiments, bezafibrate, a synthetic ligand of PPARα, was used to treat the same mouse models (Wenz et al., 2008; Viscomi et al., 2011) and also a third mouse model, the Deletor mouse containing a dominant mutation in the Twinkle helicase (Yatsuga and Suomalainen, 2012).
For ligand elongation we inserted two, three or four Ig domains from human CD2, mouse CD22 containing a mutation that makes it non-functional and human CD4, respectively.
An in vivo interaction between Myb and p300 was revealed by the identification of the plt6 mouse strain containing a mutation in the KIX domain.
We applied a proteomic approach to a mouse strain containing a null mutation of the Ugt1 gene with the aim of shedding light on the mechanisms and molecular effectors involved in bilirubin-associated neurotoxicity in vivo.
To distinguish the functions of secreted BMP2 from nBMP2, we generated a mouse strain containing a targeted mutation in which the conventional growth factor BMP2 is secreted and signals normally, but nBMP2 is excluded from the nucleus by means of a three-amino-acid substitution in the nuclear localization signal [ 2].
Unlike the AF1 mutation, diarylheptanoids (D1, D2, and D3) and E2 both failed to stimulate ERE-dependent luciferase activity of the mouse ERα containing two-point mutations in its AF2 domain (mAF2ER).
We thus studied the human SupT1 T-cell line with intensified RNAi developed by Llano et al. [37], and mouse cells containing homozygous gene trap mutations at the LEDGF/p75 locus developed by Sutherland and coworkers [42].
Chimeric males derived by injecting ES cells into blastocysts were used to establish mouse lines containing the desired point mutations as well as the floxed NeoR cassette used for ES cell selection.
When poly I C challenges were made in triple transgenic mice containing mutations in APP, PS1 and Tau, inflammation induced APP fragments to act as a seeding point for senile human-like Aβ deposits and drove Tau tangle-like structures in neuronal somata, thus recapitulating two key features of human disease, with systemic inflammation as a driver.
