High Expression Of Atp7b MRNA In The Peripheral Blood Mononuclear Cells Of The Long-Evans Cinnamon Rats: An Animal Model Of Wilsons Disease

Kenji Nakayama

doi:10.4172/2161-1041.1000115

Abstract

The Long-Evans Cinnamon (LEC) rat is an animal model of Wilson’s disease. The rat has a mutation in the copper (Cu)-transporting P-type ATPase (Atp7b) gene that is homologous to the human Wilson’s disease gene, ATP7B. The LEC rat shows all of the biochemical features of the disease. In this study, we focused on the expression levels of mutant Atp7b mRNAs in the peripheral blood mononuclear cells (PBMCs) of the LEC rats. Using quantitative real-time polymerase chain reaction (quantitative RT-PCR), we analyzed the expression levels of Atp7b mRNAs in the PBMCs cells of both the LEC rats and Long-Evans Agouti (LEA) rats, the latter being utilized as a control for the LEC rat. At the ages of 5 and 8 weeks, the inductions of Atp7b mRNA were manifested in the PBMCs of both male and female LEC rats, while their levels in the livers were significantly lower than those of the LEA rats. These results suggest the diversity of cell-physiological and endocrinological Cu metabolisms between the PBMCs and the livers of the LEC rats. Our findings indicate the possibility of a novel Cu metabolism in the cardiovascular network that is concerned with Atp7b of the PBMCs.

Highlights

Wilson’s disease (WND, OMIM 277900) is an autosomal recessive disorder of copper (Cu) transport characterized by impaired incorporation of Cu into ceruloplasmin (Cp) and by impaired excretion of Cu via the bile
The levels in the Long-Evans Cinnamon (LEC) rat livers at the age of 8 weeks reduced to 0.31 and to 0.50 against the controls in males and females, respectively. These results suggest that a part of mutant Atp7b mRNA exists in the LEC rat livers while it was significantly down-regulated compared to the controls
We focused on the expression level of Atp7b mRNA in the peripheral blood mononuclear cells (PBMCs) of the LEC rats

Summary

Introduction

Wilson’s disease (WND, OMIM 277900) is an autosomal recessive disorder of copper (Cu) transport characterized by impaired incorporation of Cu into ceruloplasmin (Cp) and by impaired excretion of Cu via the bile. The disease phenotype includes progressive hepatic degeneration and/or neurological impairment as a result of the toxic effects of accumulated Cu in several tissues, principally the liver and brain. The high prevalence (1:10,000) of WND in Japan strongly supports our previous report [7]: one WND patient at the presymptomatic stage was detected through the analyses of 11,362 child subjects using the automated urinary Cp assay at the mandatory medical health care examination for 3-year-old children. Our attempt was to succeed for the first time in early and presymptomatic diagnosis of WND in conjunction with the mandatory medical health care program at the age of 3 years

Methods

Results

Conclusion