Pathology of Spontaneous Dermatitis in CBy.ALY-aly Mice

Kobayashi, Shinobu; Ueda, Akiko; Ueda, Makoto; Nawa, Kouji

doi:10.1538/expanim.57.159

Cited by 4 publications

(3 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Eosinophilic infiltrations were accompanied by progressive changes in organ architecture and fibrosis, most likely a consequence of toxic mediators produced by eosinophils, such as eosinophil peroxidase or MBP (45, 46). Two earlier histological studies had described organ-specific eosinophilic infiltration in the stroma of the epididymis/ vas deferens (47) and in the skin (48) in Nik aly/aly mice, rather than revealing the general inflammation apparent in the Nik −/− mice described here. Whether these disparities reflect an incomplete defect of the signaling function of Nik aly/aly , which harbors a point mutation in the C-terminal part of NIK that contributes to IKKα binding (21, 49), or reflects the more restricted scope of mentioned studies is currently unclear.…”

Section: Discussionmentioning

confidence: 50%

NIK Prevents the Development of Hypereosinophilic Syndrome-like Disease in Mice Independent of IKKα Activation

Chi

Rehg

Redecke

2012

The Journal of Immunology

View full text Add to dashboard Cite

Immune cell-mediated tissue injury is the common feature of different inflammatory diseases, yet the pathogenetic mechanisms and cell types involved vary significantly. Hypereosinophilic Syndrome (HES) represents a group of inflammatory diseases that are characterized by increased numbers of pathogenic eosinophilic granulocytes in the peripheral blood and diverse organs. Based on clinical and laboratory findings, various forms of HES have been defined, yet the molecular mechanism and potential signaling pathways that drive eosinophil expansion remain largely unknown. Here we show that mice deficient of the serine/ threonine-specific protein kinase NF-κB inducing kinase (NIK) develop a HES-like disease, reflected by progressive blood and tissue eosinophilia, tissue injury and premature death at around 25–30 weeks of age. Similar to the lymphocytic form of HES, CD4+ T-cells from NIK-deficient mice express increased levels of T-helper 2 (Th2)-associated cytokines, and eosinophilia and survival of NIK deficient mice could completely be prevented by genetic ablation of CD4+ T-cells. Experiments based on bone marrow chimeric mice, however, demonstrated that inflammation in NIK-deficient mice depended on radiation-resistant tissues, implicating that NIK-deficient immune cells mediate inflammation in a non-autonomous manner. Surprisingly, disease development was independent of NIKs known function as IkappaB kinase (IKK)-α kinase, as mice carrying a mutation in the activation loop of IKKα, which is phosphorylated by NIK, did not develop inflammatory disease. Our data show that NIK activity in non-hematopoietic cells controls Th2-cell development and prevents eosinophil-driven inflammatory disease, most likely using a signaling pathway that operates independent of the known NIK substrate IKKα.

show abstract

Section: Discussionmentioning

confidence: 50%

NIK Prevents the Development of Hypereosinophilic Syndrome-like Disease in Mice Independent of IKKα Activation

Chi

Rehg

Redecke

2012

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In addition, aly/aly mice also develop inflammatory lesions in the kidneys, lungs and exocrine tissues of the pancreas. For this reason, aly/aly mice have been used more frequently for studies of other conditions including pancreatitis, dermatitis and osteoporosis [115–117]. Histologically, mononuclear infiltrates, primarily consisting of CD4+ cells, invade into periductal regions and frequently extend into acinar lobules.…”

Section: Mouse Modelsmentioning

confidence: 99%

Mouse Models of Primary Sjogren’s Syndrome

Park¹,

Gauna²,

Cha

2015

CPD

View full text Add to dashboard Cite

Sjögren’s syndrome (SjS) is a chronic autoimmune disorder characterized by immune cell infiltration and progressive injury to the salivary and lacrimal glands. As a consequence, patients with SjS develop xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). SjS is the third most common rheumatic autoimmune disorder, affecting 4 million Americans with over 90% of patients being female. Current diagnostic criteria for SjS frequently utilize histological examinations of minor salivary glands for immune cell foci, serology for autoantibodies, and dry eye evaluation by corneal or conjunctival staining. SjS can be classified as primary or secondary SjS, depending on whether it occurs alone or in association with other systemic rheumatic conditions, respectively. Clinical manifestations typically become apparent when the disease is relatively advanced in SjS patients, which poses a challenge for early diagnosis and treatment of SjS. Therefore, SjS mouse models, because of their close resemblance to the human SjS, have been extremely valuable to identify early disease markers and to investigate underlying biological and immunological dysregulations. However, it is important to bear in mind that no single mouse model has duplicated all aspects of SjS pathogenesis and clinical features, mainly due to the multifactorial etiology of SjS that includes numerous susceptibility genes and environmental factors. As such, various mouse models have been developed in the field to try to recapitulate SjS. In this review, we focus on recent mouse models of primary SjS and describe them under three categories of spontaneous, genetically engineered, and experimentally induced development of SjS-like disease. In addition, we discuss future perspectives of SjS mouse models highlighting pros and cons of utilizing mouse models and demands for improved models.

show abstract

“…However, there are no detectable autoantibodies against nuclear components or salivary gland proteins in the serum of aly/aly mice (72). Notably, aly/aly mice develop systemic disease that can involve multiple organs, and they are also used as animal models for pancreatitis (73), dermatitis (74), and osteoporosis (75).…”

Section: Aly/aly Micementioning

confidence: 99%

Recent Advances in Mouse Models of Sjögren's Syndrome

et al. 2020

View full text Add to dashboard Cite

Sjögren's syndrome (SS) is a complex rheumatoid disease that mainly affects exocrine glands, resulting in xerostomia (dry mouth) and xerophthalmia (dry eye). SS is characterized by autoantibodies, infiltration into exocrine glands, and ectopic expression of MHC II molecules on glandular epithelial cells. In contrast to the well-characterized clinical and immunological features, the etiology and pathogenesis of SS remain largely unknown. Animal models are powerful research tools for elucidating the pathogenesis of human diseases. To date, many mouse models of SS, including induced models, in which disease is induced in mice, and genetic models, in which mice spontaneously develop SS-like disease, have been established. These mouse models have provided new insight into the pathogenesis of SS. In this review, we aim to provide a comprehensive overview of recent advances in the field of experimental SS.

show abstract

Pathology of Spontaneous Dermatitis in CBy.ALY-aly Mice

Abstract: Abstract:CBy. ALY-aly/aly (C-aly)

Cited by 4 publications

References 9 publications

NIK Prevents the Development of Hypereosinophilic Syndrome-like Disease in Mice Independent of IKKα Activation

NIK Prevents the Development of Hypereosinophilic Syndrome-like Disease in Mice Independent of IKKα Activation

Mouse Models of Primary Sjogren’s Syndrome

Recent Advances in Mouse Models of Sjögren's Syndrome

Contact Info

Product

Resources

About