Adipose-specific RAPTOR knockout mice show similar properties with those long-lived mice, including increased leanness and resistance to diet-induced obesity accompanied by improved glucose tolerance and insulin sensitivity (Polak and Hall, 2009).
Overexpression of SIRT1 in transgenic mice confers many of the same phenotypes as CR in mice, including increased performance in a rotarod assay [ 19].
Other abnormalities reported in CRND8 mice included increased stereotypic behavior [ 29], brain inflammation [ 30] and increased sensitivity to experimentally induced seizures [ 31].
As summarized in Fig. 8, changes occurring during early cachexia in C-26-tumor-bearing mice included increased inflammation, metabolic alterations, enhanced muscle fatigability and reduced grip strength.
However, there was clear evidence of carcinogenic activity due to isoeugenol in male B6C3F1 mice, including increased incidence of hepatocellular adenoma, hepatocellular carcinoma, and hepatocellular adenoma with carcinoma.
Stimulation of inflammation also recapitulates many AD features in mice, including increased levels of cleaved APP fragments, altered tau phosphorylation [ 143] and declining motor and cognitive skills.
Additional characteristics observed in Atg16L1HM mice included increased inflammation in the muscularis and associated mesenteric fat and blood vessels, increases in lymphoid aggregates, subserosal fibrosis, hypertrophy of the muscularis propria and proximal epithelial hyperplasia.
Various experiments revealed behavioral abnormalities in these mice, including increased depression-like and disinhibition-like behavior, in addition to impaired cognitive behavior in older animals, all of which are behavioral phenotypes observed in FTLD patients [ 72].
μCT scanning also revealed several other skeletal abnormalities in ptpn11 fl/fl ert2-cre mice, including increased rib thickness, evidence of previous rib fractures and the presence of ectopic calcified growths on ribs (Fig. 4C and data not shown).
Analysis of TLQP21-treated mice revealed a phenotype with numerous additional similarities to VGF knockout mice including increased energy expenditure, increased WAT β2-adrenergic receptor mRNA levels, increased WAT UCP1 mRNA levels, normal locomotor activity, and decreased WAT weight {see Results and [ 21]}.
