Novel recombinant congenic mouse strain developing arthritis with enthesopathy

Mori, Shiro; Tanda, Naoko; Ito, Meiichi; Oishi, Hisashi; Tsubaki, Takahito; Komori, H.; Zhang, Ming Cai; Ono, M.; Nishimura, Masahiko; Nose, Masato

doi:10.1111/j.1440-1827.2008.02245.x

Cited by 7 publications

(9 citation statements)

References 21 publications

(20 reference statements)

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“…However, these mice mainly exhibit fibrous proliferation in enthesis and fibrous ankylosis, without erosion and bone destruction [29]. McH/lpr-RA1 mice show synovitis, pannus formation and ankylosis, resembling spondyloarthritis [12]. We consider that McH/lpr-RA1 mice are a suitable experimental disease model of spondyloarthritis.…”

Section: Discussionmentioning

confidence: 99%

“…McH/lpr-RA1 mice were generated using F54 C3H/HeJ- lpr / lpr and MRL/lpr × (MRL/lpr × C3H/lpr) mice. This recombinant congenic strain of mice was designated McH/lpr-RA1 as previously described in the literature [12]. All mice were housed in the animal unit of Tohoku University Medical School, an environmentally controlled and specific pathogen-free facility.…”

Section: Methodsmentioning

confidence: 99%

“…Our research group have previously reported the development of a murine model with spontaneous, progressive ankylosis in ankle joints [12]. Backcross generation mice were prepared using a non-arthritis strain of mice, C3H/HeJ-lpr/lpr (C3H/lpr), MRL/lpr × (MRL/lpr × C3H/lpr) F1.…”

Section: Introductionmentioning

confidence: 99%

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The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed ankylosing arthritis

Izumiyama

Mori

Takeda³

et al. 2018

Preprint

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Abstract[Background]McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop arthritis in the ankle, leading finally to ankylosis. There is no published data that drug treatment has been trialed on these mice.[Objectives]This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16-1, for the treatment of ankylosis in McH-lpr/lpr-RA1 mice.[Methods]Male McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16-1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines.[Results]Tissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the control group at every age. The kappa coefficient was 0.77. However, progression of ankylosis persisted in the MR16-1 treated group. In vivo imaging using indocyanine green liposomes showed significant decreases in signal intensities of treated groups at week 14, but no significant differences were observed at week 18. Blood serum amyloid A levels in treated groups were significantly lower at 17 weeks of age. The gene expression levels of Tnf and Il17 were also significantly lower in MR16-1 treated groups.[Conclusions]Administration of the anti-IL-6 receptor antibody is effective for the treatment of synovitis and bone destruction of McH-lpr/lpr-RA1 mice. McH-lpr/lpr-RA1 mice may be a suitable experimental model for the development of new treatments for spondyloarthritis. IL6 signal blockade could contribute to the treatment of spondyloarthritis, and further studies should be carried out to confirm its potential in the prevention of deformity associated with ankylosis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed ankylosing arthritis

Izumiyama

Mori

Takeda³

et al. 2018

Preprint

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“…5b). 50 The mice revealed severe granulomatous synovitis and also fibrous and fibrocartilaginous lesions of articular ligamenta resembling enthesopathy, resulting in ankylosis. This may indicate that a particular genome recombination with that of C3H/lpr mice induced severe arthritis leading to ankylosis, which is not developed by an MRL/lpr genome alone.…”

Section: Genetic Segregation Of Pathological Manifestations Of Collagmentioning

confidence: 99%

A polygene network model for the complex pathological phenotypes of collagen disease

Nose

2011

Pathology International

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Almost 70 years after the description of 'collagen disease' by P. Klemperer et al., it is still controversial whether the diversity and similarity of pathological manifestations among the collagen diseases depends on ambiguity in diagnosis or is an intrinsic quality of the collagen diseases themselves. A genome wide analysis of the MRL mouse models of collagen disease may shed some light on the complex pathological manifestations. Study of the susceptibility loci to each type ofcollagen disease (such as glomerulonephritis, vasculitis, arthritis, sialoadenitis and dacryoadenitis) in the mice, revealed that these lesions developed because of a cumulative effect of multiple gene loci, none of which can induce the related phenotype alone. This may indicate that collagen disease develops in 'a polygenic system', as proposed by K. Mather in 1949. Each lesion in the mice developed because of an additive effect of the polygenes, which is also, in part, hierarchical. Some of the polygenes seemed to be common to those in other collagen diseases as well. Some of the positional candidate genes involved an allelic polymorphism in the coding or promoter regions, thus possibly causing a qualitative or quantitative difference in their function, respectively. As a result, a particular combination of the polygenes with such an allelic polymorphism may thus play a critical role in leading the cascade reaction to developing collagen disease, and also the regular variation in the pathological manifestations. We herein describe this as a polygene network of collagen disease.

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“…Three types of mice were used: 40 BALB/c mice, 5 McH/lpr-RA1 mice with arthritis and vasculitis disease (19), and 3 C57BL/10-mdx Jic mice with muscular dystrophy. The mice were housed in the Animal Research Institute of Tohoku University Graduate School of Medicine under specific pathogen-free conditions and had free access to food and water until the beginning of the experiments.…”

Section: Animal Modelsmentioning

confidence: 99%

Delivery of Na/I Symporter Gene into Skeletal Muscle Using Nanobubbles and Ultrasound: Visualization of Gene Expression by PET

Watanabe¹,

Horie²,

Funaki³

et al. 2010

J Nucl Med

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The development of nonviral gene delivery systems is essential in gene therapy, and the use of a minimally invasive imaging methodology can provide important clinical endpoints. In the current study, we present a new methodology for gene therapy-a delivery system using nanobubbles and ultrasound as a nonviral gene delivery method. We assessed whether the gene transfer allowed by this methodology was detectable by PET and bioluminescence imaging. Methods: Two kinds of reported vectors (luciferase and human Na/I symporter [hNIS]) were transfected or cotransfected into the skeletal muscles of normal mice (BALB/c) using the ultrasound-nanobubbles method. The kinetics of luciferase gene expression were analyzed in vivo using bioluminescence imaging. At the peak of gene transfer, PET of hNIS expression was performed using our recently developed PET scanner, after 124 I injection. The imaging data were confirmed using reverse-transcriptase polymerase chain reaction amplification, biodistribution, and a blocking study. The imaging potential of the 2 methodologies was evaluated in 2 mouse models of human pathology (McH/lpr-RA1 mice showing vascular disease and C57BL/10-mdx Jic mice showing muscular dystrophy). Results: Peak luciferase gene activity was observed in the skeletal muscle 4 d after transfection. On day 2 after hNIS and luciferase cotransfection, the expression of these genes was confirmed by reverse-transcriptase polymerase chain reaction on a muscle biopsy. PET of the hNIS gene, biodistribution, the blocking study, and autoradiography were performed on day 4 after transfection, and it was indicated that hNIS expression was restricted to the site of plasmid administration (skeletal muscle). Similar localized PET and 124 I accumulation were successfully obtained in the diseasemodel mice. Conclusion: The hNIS gene was delivered into the skeletal muscle of healthy and disease-model mice by the ultrasound-nanobubbles method, and gene expression was successfully visualized with PET. The combination of ultrasound-nanobubble gene transfer and PET may be applied to gene therapy clinical protocols.

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Novel recombinant congenic mouse strain developing arthritis with enthesopathy

Cited by 7 publications

References 21 publications

The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed ankylosing arthritis

The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed ankylosing arthritis

A polygene network model for the complex pathological phenotypes of collagen disease

Delivery of Na/I Symporter Gene into Skeletal Muscle Using Nanobubbles and Ultrasound: Visualization of Gene Expression by PET

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