Human Disease Model Report: prion diseases

General Information

Name

prion diseases

FlyBase ID

FBhh0000185

Disease Ontology Term

prion disease

Parent Disease

OMIM

Overview

The human PRNP gene encodes the prion protein, which has been implicated in various types of transmissible neurodegenerative spongiform encephalopathies. Approximately 15% of human prion diseases are inherited; these include familial Creutzfeldt-Jakob disease (MIM:123400; FBhh0000791), Gerstmann-Straussler disease (MIM:137440, FBhh0000184), fatal familial insomnia (MIM:600072, FBhh0000914), and others (see MIM:176640). No gene orthologous to PRNP has been identified in Drosophila.

Experiments using the human Hsap\PRNP gene have made use of UAS constructs carrying the variants V129 or M129. Expression of these constructs in the fly adult eye results in a severe and easily scored eye phenotype, allowing assessment of genetic interactions. Structural abnormalities in the adult brain are also observed. PRNP:p.M129 , when homozygous, may increase risk of sporadic Creutzfeldt-Jakob disease. Flies were not observed to generate toxic prions spontaneously, consistent with the idea that neurotoxicity is caused by different conformations of transmissible Hsap\PRNP.

Prion diseases have been investigated in flies by transgenic introduction of prion protein genes from a number of mammalian species, including mouse (FlyBase record Mmus\Prnp), hamster (FlyBase record Maur\Prp), rabbit (FlyBase record Ocun\PRNP), sheep (FlyBase record Oari\PrP), dog (FlyBase record Cfam\PRNP), horse (FlyBase record Ecab\PRNP) and cow (FlyBase record Btau\PRNP).

Using mouse and hamster genes, variants associated with Creutzfeldt-Jakob disease, a variant associated fatal familial insomnia, and a variant associated with Gerstmann-Straussler disease have been characterized in flies. See the 'Disease-Implicated Variants' table, below.

Protective variants have been identified in dog (D159 in Cfam\PRNP), in horse (S167 in Ecab\PRNP), and in rabbit (S174 in Ocun\PRNP). Mix-and-match studies (introduction of a protective variant into a vulnerable type and vice-versa) have been conducted in flies.

The bovine transgenic model has been used as (relatively) rapid prion bioassay system.

[updated May 2022 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: prion diseases

OMIM report

Symptoms and phenotype

The human prion diseases occur in inherited, acquired, and sporadic forms. Approximately 15% are inherited and associated with coding mutations in the PRNP gene. Inherited prion diseases include familial Creutzfeldt-Jakob disease (CJD; MIM:123400), Gerstmann-Straussler disease (GSD; MIM:137440), and fatal familial insomnia (FFI; MIM:600072). Acquired prion diseases in humans include iatrogenic CJD, kuru (MIM:245300), and variant CJD (vCJD). Variant CJD is believed to be acquired from cattle infected with BSE. The majority of human cases of prion disease occur as sporadic CJD (sCJD) (Collinge et al., 1996, pubmed:8878476; Parchi et al., 2000, pubmed:10963679; Hill et al., 2003, pubmed:12764055). [from MIM:176640; 2016.03.01]

(OMIM, 2013-)

Genetics

The PRNP gene encodes the prion protein, which has been implicated in various types of transmissible neurodegenerative spongiform encephalopathies. [from MIM:176640; 2016.03.01]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

The protein encoded by PRNP is a membrane glycoprotein that tends to aggregate into rod-like structures. Its primary physiological function is unclear; may be required for neuronal myelin sheath maintenance (Bremer et al, 2010, pubmed:20098419); may have cytoprotective activity against internal or environmental stresses. [from Gene Cards, PRNP; 2016.03.01]

(FlyBase Curators, 2013-)

External links