Table 3.

Limitations of murine models

Limitations of Murine Models	Description
Interspecies Differences	Human genome is larger than the mouse genome by 14% (2.9 vs 2.5 Gb) (Mouse Genome Sequencing et al. 2002) Genes implicated in reproduction, immunity, and olfaction vary with an estimated 300 genes differing between species (Mouse Genome Sequencing et al. 2002) Differences in innate and adaptive immunity (Table 4)
Differences Between Strains	Highly inbred strains are well-characterized while outbred strains are ill-defined C57BL/6 mice have a TH1-predominant response while other strains like BALB/c, A/J, and DBA/2 mice exhibit a TH2-predominant response (Mills et al. 2000; Sellers et al. 2012)
Effect of the Environment	Laboratory mice housed in specific pathogen-free barrier facilities and hence have an immature immune system similar to that of a neonate with a paucity of memory T cells (Beura et al. 2016)
Age	Young mice (6–10 weeks old) which are equivalent to teenage adults are used to represent an often elderly human population Limited availability of aged mice Lack of correlation of the blood leukocyte transcriptomic response between species despite adjusting for age using aged mice (Gentile et al. 2014b)
Gender	Predominant use of male mice in sepsis and trauma models Evidence to suggest hormonal differences may impact survival in sepsis (Kher et al. 2005; Knöferl et al. 2002; Merkel et al. 2001; Zellweger et al. 1997)
Mouse Homogeneity	Highly inbred mice may not accurately represent the genetically diverse human population
Comorbid Disease	While comorbid disease is prevalent within the human population, it is not well represented in mouse models No murine model is able to reproduce induced frailty and the chronic low-grade organ dysfunction that occurs following sepsis and trauma
Ability to Provide Supportive Care	Limited ability to perform hemodynamic monitoring in the mouse Unable to administer supportive care measures to possibly correct organ failure including mechanical ventilation, renal replacement therapy, infusion of vasopressors, surgical source control, and delivery of enteral or parenteral nutrition (Fink 2014)
Mismatch in Disease Severity and Temporal Response	Murine models of trauma often involve a single organ and are not multi-compartmental, unlike the majority of human trauma Sepsis develops over hours to days in humans while it progresses more rapidly in mice (Buras et al. 2005; Deitch 1998)
Variability within Murine Models	No uniform consensus as to which models are best Magnitude of inflammatory response differs between various murine models of sepsis (Maier et al. 2004)