Mouse Models of Food Allergy: How Well do They Simulate the Human Disorder?

The prevalence of IgE-mediated food allergies has increased dramatically in the past three decades, now affecting up to 10% of the US population. IgE-mediated food allergy is an immunologic disease, involving a variety of cells, including B and T cells, mast cells, basophils, ILC2s, and epithelial cells. Mouse models of food allergy mimic the overall immunologic processes known to exist in humans. Due to the limitations of invasive sampling of human tissue and the similarities of the human and mouse immune systems, comprehensive pathogenesis studies of food allergy have been performed in mouse models. Mouse models have been effective in elucidating the roles of non-oral routes of sensitization and identifying key cells and molecules involved in allergic sensitization. Furthermore, the development of novel therapeutic approaches for food allergy has been accelerated through the use of pre-clinical mouse models. Despite the groundbreaking findings stemming from research in mice, there are continued efforts to improve the translational utility of these models. Here, we highlight the achievements in understanding food allergy development and efforts to bring novel treatment approaches into clinical trials.

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IL-10- and retinoic acid-induced regulatory dendritic cells are therapeutically equivalent in mouse models of asthma and food allergy

AIMS Allergy and Immunology ◽

10.3934/allergy.2021007 ◽

2021 ◽

Vol 5 (2) ◽

pp. 73-91

Author(s):

Chunyan Li ◽

◽

Wojciech Dawicki ◽

Xiaobei Zhang ◽

Chris Rudulier ◽

...

Keyword(s):

Dendritic Cells ◽

Food Allergy ◽

Retinoic Acid ◽

Mouse Models ◽

Regulatory Dendritic Cells

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Mouse Models of Human Claudin-Associated Disorders: Benefits and Limitations

International Journal of Molecular Sciences ◽

10.3390/ijms20215504 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5504 ◽

Cited By ~ 3

Author(s):

Murat Seker ◽

Cármen Fernández-Rodríguez ◽

Luis Martínez-Cruz ◽

Dominik Müller

Keyword(s):

Tight Junction ◽

Mouse Models ◽

Supramolecular Structure ◽

Proper Function ◽

Major Protein ◽

Complex Phenotype ◽

Adjacent Structures ◽

Phenotype Analysis ◽

Human Disorders ◽

Human Disorder

In higher organisms, epithelia separate compartments in order to guarantee their proper function. Such structures are able to seal but also to allow substances to pass. Within the paracellular pathway, a supramolecular structure, the tight junction transport is largely controlled by the temporospatial regulation of its major protein family called claudins. Besides the fact that the expression of claudins has been identified in different forms of human diseases like cancer, clearly defined mutations in the corresponding claudin genes have been shown to cause distinct human disorders. Such disorders comprise the skin and its adjacent structures, liver, kidney, the inner ear, and the eye. From the phenotype analysis, it has also become clear that different claudins can cause a complex phenotype when expressed in different organs. To gain deeper insights into the physiology and pathophysiology of claudin-associated disorders, several mouse models have been generated. In order to model human disorders in detail, they have been designed either as full knockouts, knock-downs or knock-ins by a variety of techniques. Here, we review human disorders caused by CLDN mutations and their corresponding mouse models that have been generated thus far and assess their usefulness as a model for the corresponding human disorder.

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Mouse Models of Primary Aldosteronism: From Physiology to Pathophysiology

Endocrinology ◽

10.1210/en.2017-00637 ◽

2017 ◽

Vol 158 (12) ◽

pp. 4129-4138 ◽

Cited By ~ 11

Author(s):

Leticia Aragao-Santiago ◽

Celso E Gomez-Sanchez ◽

Paolo Mulatero ◽

Ariadni Spyroglou ◽

Martin Reincke ◽

...

Keyword(s):

Mouse Models ◽

Primary Aldosteronism ◽

Genetic Basis ◽

Plasma Renin ◽

Adrenal Hyperplasia ◽

Endocrine Hypertension ◽

Bilateral Adrenal Hyperplasia ◽

Human Disorder ◽

Aldosterone Producing Adenoma ◽

Functional Mechanisms

Abstract Primary aldosteronism (PA) is a common form of endocrine hypertension that is characterized by the excessive production of aldosterone relative to suppressed plasma renin levels. PA is usually caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations have been identified in several genes that encode ion pumps and channels that may explain the aldosterone excess in over half of aldosterone-producing adenomas, whereas the pathophysiology of bilateral adrenal hyperplasia is largely unknown. A number of mouse models of hyperaldosteronism have been described that recreate some features of the human disorder, although none replicate the genetic basis of human PA. Animal models that reproduce the genotype–phenotype associations of human PA are required to establish the functional mechanisms that underlie the endocrine autonomy and deregulated cell growth of the affected adrenal and for preclinical studies of novel therapeutics. Herein, we discuss the differences in adrenal physiology across species and describe the genetically modified mouse models of PA that have been developed to date.

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Mouse Models for Food Allergies: Where Do We Stand?

Cells ◽

10.3390/cells8060546 ◽

2019 ◽

Vol 8 (6) ◽

pp. 546 ◽

Cited By ~ 8

Author(s):

Stefan Schülke ◽

Melanie Albrecht

Keyword(s):

Mast Cell ◽

Food Allergy ◽

Immune Responses ◽

Mouse Models ◽

Mast Cell Activation ◽

Food Allergies ◽

Mouse Strains ◽

Skin Reactions ◽

Human Pathology ◽

Th2 Responses

Food allergies are a steadily increasing health and economic problem. Immunologically, food allergic reactions are caused by pathological, allergen-specific Th2 responses resulting in IgE-mediated mast cell degranulation and associated inflammatory reactions. Clinically, food allergies are characterized by local inflammation of the mouth mucosa, the face, the throat, the gastrointestinal tract, are frequently paralleled by skin reactions, and can result in life-threatening anaphylactic reactions. To better understand food allergies and establish novel treatment options, mouse models are indispensable. This review discusses the available mouse food allergy models, dividing them into four categories: (1) adjuvant-free mouse models, (2) mouse models relying on adjuvants to establish allergen-specific Th2 responses, (3) mouse models using genetically-modified mouse strains to allow for easier sensitization, and (4) humanized mouse models in which different immunodeficient mouse strains are reconstituted with human immune or stem cells to investigate humanized immune responses. While most of the available mouse models can reproducibly portray the immunological parameters of food allergy (Th2 immune responses, IgE production and mast cell activation/expansion), so far, the recreation of the clinical parameters has proven more difficult. Therefore, up to now none of the available mouse models can reproduce the complete human pathology.

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