B6-hCD20 Mice

Catalog Number: C001625

Strain Name: C57BL/6NCya-Ms4a1em1(hMS4A1)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

Cluster of Differentiation 20 (CD20), encoded by the membrane spanning 4-domains A1 (MS4A1) gene, is a transmembrane phosphoprotein primarily expressed on the surface of B cells. Throughout B cell development, from pro-B cell to memory B cell stages, CD20 is expressed, but is absent in early pro-B cells and plasma cells [1]. Belonging to the MS4A family of four-transmembrane domain proteins, CD20 modulates B cell activation and proliferation by regulating calcium signaling, potentially acting as a calcium channel or co-receptor to amplify B cell receptor (BCR) responses [1]. As a key biomarker for B cell malignancies, including B-cell lymphomas, chronic lymphocytic leukemia, and hairy cell leukemia, CD20 serves as a target for therapeutic monoclonal antibodies such as rituximab and obinutuzumab, enabling the depletion of pathogenic B cells in autoimmune diseases and cancers [2-3]. Disruption of MS4A1 is associated with immunodeficiency common variable type 5 (CVID5), characterized by hypogammaglobulinemia, recurrent infections, and impaired antibody production due to aberrant B cell differentiation [4]. Recent studies have also revealed a role for CD20 in olfactory sensory neurons, where it mediates innate predator-avoidance behaviors in mice by detecting predator-derived odorants [5]. This dual functionality underscores the protein's significance in both immune regulation and sensory biology.

The B6-hCD20 mouse is a humanized model generated using gene editing technology to replace the entire base sequence of the mouse Ms4a1 gene in situ with the corresponding sequence from the human MS4A1 gene. Homozygous B6-hCD20 mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of autoimmune diseases and cancers, and for the screening, development and preclinical efficacy and safety evaluation of CD20-targeted drugs.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hCD20 mice. The sequence from ATG start codon to TAA stop codon of the endogenous mouse Ms4a1 gene was replaced with the sequence from ATG start codon to TAA stop codon of the human MS4A1 gene.

 

Application

  • Screening, development and preclinical efficacy and safety evaluation of CD20-targeted therapies;
  • Research on the pathological mechanisms and therapeutic approaches of autoimmune diseases and cancers.



References
[1]Pavlasova G, Mraz M. The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy. Haematologica. 2020 Jun;105(6):1494-1506.
[2]Zou L, Song G, Gu S, Kong L, Sun S, Yang L, Cho WC. Mechanism and Treatment of Rituximab Resistance in Diffuse Large Bcell Lymphoma. Curr Cancer Drug Targets. 2019;19(9):681-687. doi: 10.2174/1568009619666190126125251. PMID: 31142246.
[3]Schuster SJ, Huw LY, Bolen CR, Maximov V, Polson AG, Hatzi K, Lasater EA, Assouline SE, Bartlett NL, Budde LE, Matasar MJ, Koeppen H, Piccione EC, Wilson D, Wei MC, Yin S, Penuel E. Loss of CD20 expression as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas. Blood. 2024 Feb 29;143(9):822-832.
[4]Bisgin A, Sonmezler O, Boga I, Yilmaz M. The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID). Sci Rep. 2021 Apr 15;11:8308.
[5]Jiang HC, Park SJ, Wang IH, Bear DM, Nowlan A, Greer PL. CD20/MS4A1 is a mammalian olfactory receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators. Nat Commun. 2024 Apr 18;15:3360.