Masahiro Morimoto, Yusuke Yamada, Keisuke Okamoto, Saya Kagimoto, Masashi Sakurai, Yusuke Sakai, Moe Hasegawa, Hiroyuki Imai, Shusaku Shibutani

The Establishment of mutant mouse strain showing eosinophilia

Introduction

The establishment of mutant mouse strain showing eosinophilia. Discover the Yama mouse, a novel mutant strain exhibiting hypereosinophilia independent of IL-5 upregulation. This new animal model is crucial for studying allergic diseases and regenerative medicine.

Abstract

Eosinophilia is a pathological condition characterized by increased eosinophils in tissues and peripheral blood. The type 2 immune response causes eosinophilia, and interleukin-5 (IL-5) secreted by T helper 2 (Th2) cells is essential for increasing eosinophils. However, it is unclear whether there is another mechanism for the increase in eosinophil other than IL-5 upregulation. The present study found high eosinophils in the ICR mice and established inbred mice with hypereosinophilia, named “Yama mouse”, through brother-sister mating. The eosinophils in the peripheral blood of 6-week-old Yama mice were 30-fold higher than those in ICR mice, and Yama mice did not have visible lesions. The IL-5 expression had no significant difference in the spleen, mesenteric lymph nodes, or bone marrow of ICR and Yama mice. Yama mice revealed a mechanism for increased eosinophil counts other than that of IL-5 upregulation. Yama mice exhibit eosinophilia without artificial treatment; therefore, they are a good animal model for studying allergic diseases and regenerative medicine, in which eosinophils are important.

Review

Eosinophilia is a hallmark of type 2 immune responses and is commonly attributed to elevated interleukin-5 (IL-5) levels, which are critical for eosinophil proliferation, differentiation, and survival. The current study presents a significant advancement in the field by describing the establishment of the "Yama mouse," a novel inbred strain exhibiting constitutive hypereosinophilia. This work addresses a critical gap in our understanding, specifically by investigating mechanisms of eosinophil accumulation independent of IL-5 upregulation, thereby offering a fresh perspective on eosinophil biology with broad implications for research into allergic diseases and other eosinophil-driven pathologies. Through careful brother-sister mating, the authors successfully established the Yama mouse strain from an ICR background, revealing a striking phenotype. A robust 30-fold increase in peripheral blood eosinophils was observed in 6-week-old Yama mice compared to control ICR mice, remarkably without any visible pathological lesions. Crucially, the study demonstrates that this profound eosinophilia occurs *without* a significant difference in IL-5 expression in key lymphoid organs such as the spleen, mesenteric lymph nodes, or bone marrow. This compelling evidence strongly supports the existence of an alternative, IL-5-independent pathway or regulatory mechanism driving eosinophil expansion and survival, presenting a potential paradigm shift from the conventional IL-5-centric view. The Yama mouse represents a highly valuable addition to the toolkit for immunology and pathology research. As a model exhibiting spontaneous eosinophilia without artificial induction, it provides an unparalleled opportunity to dissect the genetic and molecular underpinnings of IL-5-independent eosinophil biology. This strain will be instrumental in studying conditions where eosinophils play a critical role, such as allergic inflammation, asthma, atopic dermatitis, parasitic infections, and in the burgeoning field of regenerative medicine where eosinophil functions are increasingly recognized. Further research leveraging this model to identify the specific genetic mutations and downstream signaling pathways responsible for the observed eosinophilia will undoubtedly advance our understanding of eosinophil homeostasis and pathogenesis.

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