. 2011 Dec; 49(1):32-43.
doi: 10.1177/0300985811429314.

Immunological variation between inbred laboratory mouse strains: points to consider in phenotyping genetically immunomodified mice

R S Sellers 1 C B Clifford  P M Treuting  C Brayton  
  • PMID: 22135019
  •     129 citations


Inbred laboratory mouse strains are highly divergent in their immune response patterns as a result of genetic mutations and polymorphisms. The generation of genetically engineered mice (GEM) has, in the past, used embryonic stem (ES) cells for gene targeting from various 129 substrains followed by backcrossing into more fecund mouse strains. Although common inbred mice are considered "immune competent," many have variations in their immune system-some of which have been described-that may affect the phenotype. Recognition of these immune variations among commonly used inbred mouse strains is essential for the accurate interpretation of expected phenotypes or those that may arise unexpectedly. In GEM developed to study specific components of the immune system, accurate evaluation of immune responses must take into consideration not only the gene of interest but also how the background strain and microbial milieu contribute to the manifestation of findings in these mice. This article discusses points to consider regarding immunological differences between the common inbred laboratory mouse strains, particularly in their use as background strains in GEM.

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Protection Elicited by Attenuated Live Yersinia pestis Vaccine Strains against Lethal Infection with Virulent Y. pestis.
Christopher K Cote, Sergei S Biryukov, +11 authors, Susan L Welkos.
Vaccines (Basel), 2021 Mar 07; 9(2). PMID: 33669472    Free PMC article.
Macrophage cytokine responses to commensal Gram-positive Lactobacillus salivarius strains are TLR2-independent and Myd88-dependent.
Sreeram Udayan, Ludovica F Buttó, +6 authors, Ken Nally.
Sci Rep, 2021 Mar 17; 11(1). PMID: 33723368    Free PMC article.
Injection Reactions after Administration of Sustained-release Meloxicam to BALB/cJ, C57BL/6J, and Crl:CD1(ICR) Mice.
Stephanie R Fuetsch, Leslie A Stewart, +4 authors, Kristin N Grimsrud.
J Am Assoc Lab Anim Sci, 2021 Jan 07; 60(2). PMID: 33402233    Free PMC article.
Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution.
Kristina V Bergersen, Ashli Barnes, +2 authors, Emma H Wilson.
Front Cell Infect Microbiol, 2021 Apr 06; 11. PMID: 33816350    Free PMC article.
NLRP6 modulates neutrophil homeostasis in bacterial pneumonia-derived sepsis.
Shanshan Cai, Sagar Paudel, +5 authors, Samithamby Jeyaseelan.
Mucosal Immunol, 2020 Nov 25; 14(3). PMID: 33230225    Free PMC article.
C(3)1-TAg in C57BL/6 J background as a model to study mammary tumor development.
Isadora F G Sena, Beatriz G S Rocha, +16 authors, Alexander Birbrair.
Histochem Cell Biol, 2021 May 19; 156(2). PMID: 34003355
Differential Immune Response Following Intranasal and Intradermal Infection with Francisella tularensis: Implications for Vaccine Development.
McKayla J Nicol, David R Williamson, David E Place, Girish S Kirimanjeswara.
Microorganisms, 2021 May 06; 9(5). PMID: 33946283    Free PMC article.
Cecal Slurry Injection in Neonatal and Adult Mice.
Jaimar C Rincon, Philip A Efron, Lyle L Moldawer, Shawn D Larson.
Methods Mol Biol, 2021 May 29; 2321. PMID: 34048005    Free PMC article.
Development of Immunotherapy Combination Strategies in Cancer.
Timothy A Yap, Eileen E Parkes, +3 authors, Hussein A Tawbi.
Cancer Discov, 2021 Apr 04; 11(6). PMID: 33811048    Free PMC article.
Recessive, gain-of-function toxicity in an APOL1 BAC transgenic mouse model mirrors human APOL1 kidney disease.
Gizelle M McCarthy, Angelo Blasio, +11 authors, Martin R Pollak.
Dis Model Mech, 2021 Aug 06; 14(8). PMID: 34350953    Free PMC article.
Germinal center hypoxia in tumor-draining lymph nodes negatively regulates tumor-induced humoral immune responses in mouse models of breast cancer.
Natalie S Firmino, Rachel A Cederberg, +6 authors, Kevin L Bennewith.
Oncoimmunology, 2021 Aug 12; 10(1). PMID: 34377597    Free PMC article.
Murine cancer cachexia models replicate elevated catabolic pembrolizumab clearance in humans.
Alyssa Marie M Castillo, Trang T Vu, +15 authors, Christopher C Coss.
JCSM Rapid Commun, 2021 Sep 14; 4(2). PMID: 34514376    Free PMC article.
Transcriptional Changes in Pulmonary Phagocyte Subsets Dictate the Outcome Following Interaction With The Fungal Pathogen Cryptococcus neoformans.
Ashlee N Hawkins, Brenden F Determann, Benjamin N Nelson, Karen L Wozniak.
Front Immunol, 2021 Oct 16; 12. PMID: 34650554    Free PMC article.
Mouse background genetics in biomedical research: The devil's in the details.
Ariel M Hay, Heather L Howie, +4 authors, James C Zimring.
Transfusion, 2021 Sep 05; 61(10). PMID: 34480352    Free PMC article.
Complement-dependent synapse loss and microgliosis in a mouse model of multiple sclerosis.
Jennetta W Hammond, Matthew J Bellizzi, +7 authors, Harris A Gelbard.
Brain Behav Immun, 2020 Mar 11; 87. PMID: 32151684    Free PMC article.
Immunopathology of RSV: An Updated Review.
Harrison C Bergeron, Ralph A Tripp.
Viruses, 2021 Dec 29; 13(12). PMID: 34960746    Free PMC article.
A Mouse Immunogenicity Model for the Evaluation of Meningococcal Conjugate Vaccines.
Arun B Arunachalam, Stacey Vile, Angel Rosas.
Front Immunol, 2022 Feb 08; 13. PMID: 35126397    Free PMC article.
The mouse resource at National Resource Center for Mutant Mice.
Cunxiang Ju, Juan Liang, +5 authors, Xiang Gao.
Mamm Genome, 2022 Feb 10; 33(1). PMID: 35138443
Upregulation of CD14 in mesenchymal stromal cells accelerates lipopolysaccharide-induced response and enhances antibacterial properties.
Matthew P Hirakawa, Nikki Tjahjono, +6 authors, Raga Krishnakumar.
iScience, 2022 Feb 11; 25(2). PMID: 35141503    Free PMC article.
Islet Lymphocytes Maintain a Stable Regulatory Phenotype Under Homeostatic Conditions and Metabolic Stress.
Jennifer C Whitesell, Robin S Lindsay, +4 authors, Rachel S Friedman.
Front Immunol, 2022 Feb 12; 13. PMID: 35145521    Free PMC article.
Tumor immunology CRISPR screening: present, past, and future.
Matthew B Dong, Kaiyuan Tang, +2 authors, Sidi Chen.
Trends Cancer, 2021 Dec 19; 8(3). PMID: 34920978    Free PMC article.
Clinically relevant preclinical animal models for testing novel cranio-maxillofacial bone 3D-printed biomaterials.
Luan P Hatt, Keith Thompson, +2 authors, Angela R Armiento.
Clin Transl Med, 2022 Feb 17; 12(2). PMID: 35170248    Free PMC article.
Genetic Background Affects the Mucosal Secretory IgA Levels, Parasite Burden, Lung Inflammation, and Mouse Susceptibility to Ascaris suum Infection.
Luciana Maria Oliveira, Denise Silva Nogueira, +12 authors, Ricardo Toshio Fujiwara.
Infect Immun, 2021 Nov 23; 90(2). PMID: 34807734    Free PMC article.
IL-17-Dependent Dysregulated Cutaneous Immune Homeostasis in the Absence of the Wiskott-Aldrich Syndrome Protein.
Katherine E Herman, Takeshi Yoshida, +4 authors, Deborah J Fowell.
Front Immunol, 2022 Mar 11; 13. PMID: 35265075    Free PMC article.
Study of Hepatitis E Virus-4 Infection in Human Liver-Chimeric, Immunodeficient, and Immunocompetent Mice.
Laura Collignon, Lieven Verhoye, +2 authors, Philip Meuleman.
Front Microbiol, 2022 Mar 18; 13. PMID: 35295314    Free PMC article.
Determining immunoglobulin-specific B cell receptor repertoire of murine splenocytes by next-generation sequencing.
Anja Werner, Simon Schäfer, +2 authors, Thomas H Winkler.
STAR Protoc, 2022 Apr 19; 3(2). PMID: 35434659    Free PMC article.