Apolipoprotein E knockout as the basis for mouse models of dyslipidemia-induced neuropathy

► We employed genetic manipulations to produce improved models of diabetic neuropathy. ► db/db and ob/ob genotypes had hyperglycemia, dyslipidemia and evidence of neuropathy. ► Apolipoprotein knockout mice had dyslipidemia, but normoglycemia and no neuropathy. ► Apolipoprotein knockout combined with db/db or ob/ob exacerbated dyslipidemia. ► Combined apolipoprotein and leptin signaling mutations did not exacerbate neuropathy.