NSG Mice Lacking Apoe : An Immunodeficient Mouse Model of Atherosclerosis

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Abstract
Murine research on atherosclerosis has been conducted largely on the C57BL/6 (B6) strain background, and most commonly, the B6.129P2‐ Apoe tm1Unc /J (B6‐ApoE KO ) 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‐ Prkdc scid Il2rg tm1Wjl /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‐ApoE KO mice develop hypercholesteremia and atherosclerosis at levels similar to B6‐ApoE KO mice. While atherosclerosis in B6‐ApoE KO mice has been widely studied in many laboratories under multiple conditions, our initial study of disease development in NSG‐ApoE KO mice was limited and future comparative studies with B6‐ApoE KO mice are necessary. NSG‐ApoE KO mice concomitantly support human cell engraftment while developing atherosclerosis, thereby making them useful to study human‐specific immune aspects.
Funding Information
  • National Institute of General Medical Sciences (3T32GM132006)
  • Jackson Laboratory

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