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Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties.

Diack AB, Ritchie DL, Peden AH, Brown D, Boyle A, Morabito L, Maclennan D, Burgoyne P, Jansen C, Knight RS, Piccardo P, Ironside JW, Manson JC - Emerging Infect. Dis. (2014)

Bottom Line: Variably protease-sensitive prionopathy (VPSPr) can occur in persons of all codon 129 genotypes in the human prion protein gene (PRNP) and is characterized by a unique biochemical profile when compared with other human prion diseases.We investigated transmission properties of VPSPr by inoculating transgenic mice expressing human PRNP with brain tissue from 2 persons with the valine-homozygous (VV) and 1 with the heterozygous methionine/valine codon 129 genotype.Some of these deposits resembled microplaques that occur in the brains of VPSPr patients.

View Article: PubMed Central - PubMed

ABSTRACT
Variably protease-sensitive prionopathy (VPSPr) can occur in persons of all codon 129 genotypes in the human prion protein gene (PRNP) and is characterized by a unique biochemical profile when compared with other human prion diseases. We investigated transmission properties of VPSPr by inoculating transgenic mice expressing human PRNP with brain tissue from 2 persons with the valine-homozygous (VV) and 1 with the heterozygous methionine/valine codon 129 genotype. No clinical signs or vacuolar pathology were observed in any inoculated mice. Small deposits of prion protein accumulated in the brains of inoculated mice after challenge with brain material from VV VPSPr patients. Some of these deposits resembled microplaques that occur in the brains of VPSPr patients. Comparison of these transmission properties with those of sporadic Creutzfeldt-Jakob disease in the same lines of mice indicated that VPSPr has distinct biological properties. Moreover, we established that VPSPr has limited potential for human-to-human transmission.

No MeSH data available.


Related in: MedlinePlus

Gliosis in transgenic mice following inoculation with brain homogenate prepared from a postmortem sample from a person with variably protease-sensitive prionopathy. A) Immunohistochemical staining for GFAP in the hippocampus of a HuVV mouse showing microplaque-like deposits. Arrows indicate areas of reactive astrocytosis. B) A serial section from the same HuVV mouse immunolabeled for PrP by using monoclonal antibody (Purified [3F4], Cambridge Bioscience, Cambridge, UK). C) Immunohistochemical staining for GFAP in the hippocampus of a HuVV mouse showing plaque-like deposits. No reactive astrocytosis is seen in the vicinity of plaques. D) A serial section from the same HuVV mouse immunolabeled for PrP by using monoclonal antibody 3F4. GFAP, glial fibrillary acid protein; HuVV, transgenic mouse expressing human PrP gene sequence coding for the valine-homozygous codon 129 genotype; PrP, prion protein. Scale bars indicate 50 μm.
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Figure 5: Gliosis in transgenic mice following inoculation with brain homogenate prepared from a postmortem sample from a person with variably protease-sensitive prionopathy. A) Immunohistochemical staining for GFAP in the hippocampus of a HuVV mouse showing microplaque-like deposits. Arrows indicate areas of reactive astrocytosis. B) A serial section from the same HuVV mouse immunolabeled for PrP by using monoclonal antibody (Purified [3F4], Cambridge Bioscience, Cambridge, UK). C) Immunohistochemical staining for GFAP in the hippocampus of a HuVV mouse showing plaque-like deposits. No reactive astrocytosis is seen in the vicinity of plaques. D) A serial section from the same HuVV mouse immunolabeled for PrP by using monoclonal antibody 3F4. GFAP, glial fibrillary acid protein; HuVV, transgenic mouse expressing human PrP gene sequence coding for the valine-homozygous codon 129 genotype; PrP, prion protein. Scale bars indicate 50 μm.

Mentions: HuVV mice were examined for evidence of astrocytic gliosis. In mice showing only plaque-like deposits of PrP, there was no association between astrocytosis and PrP deposition and no evidence of reactive astrocytosis (Figure 5). In contrast, in the HuVV mice inoculated with brain homogenate from patient UK-VV, a single mouse showed reactive astrocytosis in the vicinity of the microplaque-like deposits (Figure 5). This HuVV mouse is the same mouse that showed evidence of plaque-like and microplaque-like deposits similar to those found in humans with VPSPr.


Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties.

Diack AB, Ritchie DL, Peden AH, Brown D, Boyle A, Morabito L, Maclennan D, Burgoyne P, Jansen C, Knight RS, Piccardo P, Ironside JW, Manson JC - Emerging Infect. Dis. (2014)

Gliosis in transgenic mice following inoculation with brain homogenate prepared from a postmortem sample from a person with variably protease-sensitive prionopathy. A) Immunohistochemical staining for GFAP in the hippocampus of a HuVV mouse showing microplaque-like deposits. Arrows indicate areas of reactive astrocytosis. B) A serial section from the same HuVV mouse immunolabeled for PrP by using monoclonal antibody (Purified [3F4], Cambridge Bioscience, Cambridge, UK). C) Immunohistochemical staining for GFAP in the hippocampus of a HuVV mouse showing plaque-like deposits. No reactive astrocytosis is seen in the vicinity of plaques. D) A serial section from the same HuVV mouse immunolabeled for PrP by using monoclonal antibody 3F4. GFAP, glial fibrillary acid protein; HuVV, transgenic mouse expressing human PrP gene sequence coding for the valine-homozygous codon 129 genotype; PrP, prion protein. Scale bars indicate 50 μm.
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Related In: Results  -  Collection

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Figure 5: Gliosis in transgenic mice following inoculation with brain homogenate prepared from a postmortem sample from a person with variably protease-sensitive prionopathy. A) Immunohistochemical staining for GFAP in the hippocampus of a HuVV mouse showing microplaque-like deposits. Arrows indicate areas of reactive astrocytosis. B) A serial section from the same HuVV mouse immunolabeled for PrP by using monoclonal antibody (Purified [3F4], Cambridge Bioscience, Cambridge, UK). C) Immunohistochemical staining for GFAP in the hippocampus of a HuVV mouse showing plaque-like deposits. No reactive astrocytosis is seen in the vicinity of plaques. D) A serial section from the same HuVV mouse immunolabeled for PrP by using monoclonal antibody 3F4. GFAP, glial fibrillary acid protein; HuVV, transgenic mouse expressing human PrP gene sequence coding for the valine-homozygous codon 129 genotype; PrP, prion protein. Scale bars indicate 50 μm.
Mentions: HuVV mice were examined for evidence of astrocytic gliosis. In mice showing only plaque-like deposits of PrP, there was no association between astrocytosis and PrP deposition and no evidence of reactive astrocytosis (Figure 5). In contrast, in the HuVV mice inoculated with brain homogenate from patient UK-VV, a single mouse showed reactive astrocytosis in the vicinity of the microplaque-like deposits (Figure 5). This HuVV mouse is the same mouse that showed evidence of plaque-like and microplaque-like deposits similar to those found in humans with VPSPr.

Bottom Line: Variably protease-sensitive prionopathy (VPSPr) can occur in persons of all codon 129 genotypes in the human prion protein gene (PRNP) and is characterized by a unique biochemical profile when compared with other human prion diseases.We investigated transmission properties of VPSPr by inoculating transgenic mice expressing human PRNP with brain tissue from 2 persons with the valine-homozygous (VV) and 1 with the heterozygous methionine/valine codon 129 genotype.Some of these deposits resembled microplaques that occur in the brains of VPSPr patients.

View Article: PubMed Central - PubMed

ABSTRACT
Variably protease-sensitive prionopathy (VPSPr) can occur in persons of all codon 129 genotypes in the human prion protein gene (PRNP) and is characterized by a unique biochemical profile when compared with other human prion diseases. We investigated transmission properties of VPSPr by inoculating transgenic mice expressing human PRNP with brain tissue from 2 persons with the valine-homozygous (VV) and 1 with the heterozygous methionine/valine codon 129 genotype. No clinical signs or vacuolar pathology were observed in any inoculated mice. Small deposits of prion protein accumulated in the brains of inoculated mice after challenge with brain material from VV VPSPr patients. Some of these deposits resembled microplaques that occur in the brains of VPSPr patients. Comparison of these transmission properties with those of sporadic Creutzfeldt-Jakob disease in the same lines of mice indicated that VPSPr has distinct biological properties. Moreover, we established that VPSPr has limited potential for human-to-human transmission.

No MeSH data available.


Related in: MedlinePlus