Expression of rabbit C-reactive protein in transgenic mice

We showed earlier that experimental autoimmune encephalomyelitis (EAE) in human C-reactive protein (CRP) transgenic mice (CRPtg) has delayed onset and reduced severity compared to wild-type mice. Since human CRP is known to engage Fc receptors and Fc receptors are known to play a role in EAE in the mouse, we sought to determine if FcRI, FcRIIb, or FcRIII was needed to manifest human CRP-mediated protection of CRPtg. We report here that in CRPtg lacking either of the two activating receptors, FcRI and FcRIII, the beneficial effects of human CRP are still observed. In contrast, if CRPtg lack expression of the inhibitory receptor FcRIIB, then the beneficial effect of human CRP is abrogated. Also, subcutaneous administration of purified human CRP stalled progression of ongoing EAE in wild-type mice, but similar treatment failed to impede EAE progression in mice lacking FcRIIB. The results reveal that a axis is responsible for protection against EAE in the CRPtg model.

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Hepatic but Not CNS-Expressed Human C-Reactive Protein Inhibits Experimental Autoimmune Encephalomyelitis in Transgenic Mice

Autoimmune Diseases ◽

10.1155/2015/640171 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Tyler T Wright ◽

Rachel V. Jimenez ◽

Todd E. Morgan ◽

Namrata Bali ◽

Xiaogang Hou ◽

...

Keyword(s):

Experimental Autoimmune Encephalomyelitis ◽

Transgenic Mice ◽

Gene Promoter ◽

C Reactive Protein ◽

Autoimmune Encephalomyelitis ◽

Reactive Protein ◽

Protective Actions ◽

Dependent Protein ◽

Low Levels ◽

Experimental Autoimmune

We recently demonstrated that human C-reactive protein (CRP), expressed hepatically in transgenic mice (CRPtg), improved the outcome of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The liver is the primary site of CRP synthesis in humans and in CRPtg mice but is also expressed by both at low levels in the CNS. To determine if CNS expression of human CRP is sufficient to impact EAE, we generated neuronal CRP transgenic mice (nCRPtg) wherein human CRP expression is driven by the neuron-specific Ca2+/calmodulin-dependent protein kinase IIα(CaMKIIα) gene promoter. We found that hepatically expressed/blood-borne CRP, but not CNS expressed CRP, lessened EAE severity. These outcomes indicate that the protective actions of human CRP in EAE are manifested in the periphery and not in the CNS and reveal a previously unappreciated site specificity for the beneficial actions of CRP in CNS disease.

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A Selective Inhibitor of Human C-reactive Protein Translation Is Efficacious In Vitro and in C-reactive Protein Transgenic Mice and Humans

Molecular Therapy — Nucleic Acids ◽

10.1038/mtna.2012.44 ◽

2012 ◽

Vol 1 ◽

pp. e52 ◽

Cited By ~ 23

Author(s):

Nicholas R Jones ◽

Melissa A Pegues ◽

Mark A McCrory ◽

Walter Singleton ◽

Claudette Bethune ◽

...

Keyword(s):

Transgenic Mice ◽

Protein Translation ◽

Selective Inhibitor ◽

C Reactive Protein ◽

Reactive Protein

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Effects of Antisense Oligonucleotides against C-Reactive Protein on the Development of Atherosclerosis in WHHL Rabbits

Mediators of Inflammation ◽

10.1155/2014/979132 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Qi Yu ◽

Zhengcao Liu ◽

Ahmed Bilal Waqar ◽

Bo Ning ◽

Xianghong Yang ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Transgenic Mice ◽

Plasma Levels ◽

Antisense Oligonucleotides ◽

C Reactive Protein ◽

Reactive Protein ◽

Atherosclerotic Lesions

Increased plasma levels of C-reactive protein (CRP) are closely associated with cardiovascular diseases, but whether CRP is directly involved in the pathogenesis of atherosclerosis is still under debate. Many controversial and contradictory results using transgenic mice and rabbits have been published but it is also unclear whether CRP lowering can be used for the treatment of atherosclerosis. In the current study, we examined the effects of the rabbit CRP antisense oligonucleotides (ASO) on the development of atherosclerosis in WHHL rabbits. CRP ASO treatment led to a significant reduction of plasma CRP levels; however, both aortic and coronary atherosclerotic lesions were not significantly changed compared to those of control WHHL rabbits. These results suggest that inhibition of plasma CRP does not affect the development of atherosclerosis in WHHL rabbits.

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