NSG Mice Lacking Apoe: An Immunodeficient Mouse Model of Atherosclerosis

Murine research on atherosclerosis has been conducted largely on the C57BL/6 (B6) strain background, and most commonly, the B6.129P2-Apoetm1Unc/J (B6-ApoEKO) strain. The use of the B6 background strain limits translatability for immunotherapy development due to inherent species differences between human and mouse immune systems. A proposed solution to this limitation is a humanized mouse model of atherosclerosis that would support the engraftment of human lymphoid and myeloid cell populations. The development of such a model has been hindered by the lack of a mouse strain that both develops atherosclerosis and supports human immune cell engraftment. In this paper, we report on a NOD.Cg-PrkdcscidIl2rgtm1Wjl/Sz (NSG) immunodeficient mouse strain that has a 383 bp deletion in the Apoe gene which prevents ApoE protein expression. When maintained on a high fat diet, NSG-ApoEKO mice develop hypercholesteremia and atherosclerosis at levels similar to B6-ApoEKO mice. While atherosclerosis in B6-ApoEKO mice has been widely studied in many laboratories under multiple conditions, our initial study of disease development in NSG-ApoEKO mice was limited and future comparative studies with B6-ApoEKO mice are necessary. NSG-ApoEKO mice concomitantly support human cell engraftment while developing atherosclerosis, thereby making them useful to study human-specific immune aspects.