NR ATKI
AU Griffiths,P.C.; Plater,J.M.; Rice,P.B.; Field,M.E.; Hazelby,O.J.; Sallis,R.E.; Farrelly,S.S.J.; Johnson,L.; Spiropoulos,J.; Windl,O.
TI Spontaneous neurological disease in transgenic bovine PrP mice
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Diagnosis DIA-20
PT Konferenz-Poster
AB
Research carried out at VLA is aimed at the preparation of more sensitive bioassay models for the detection and differentiation of BSE and scrapie agents. Susceptible and sensitive transgenic PrP mouse lines could be used to reduce, or replace, the use of conventional mouse lines as bioassay in wild-type mice is often inefficient and time consuming. In this laboratory, transgenic lines overexpressing bovine, kudu and sheep PrPs are being characterised and then challenged with BSE and scrapie to assess their suitability as improved bioassay models.
One of the transgenic bovine PrP lines produced, Tg(BoPrP)2078, showed development of spontaneous neurological disease in mice from 3-4 months of age. Initial clinical signs included affected gait and nervousness, leading to more severe motor impairment of hindlimbs and weight loss from 7 months of age. Western blotting studies revealed a high level of overexpression of the transgene in brain (50x normal), and in heart and hindlimb skeletal muscle. Pathological investigations revealed myofibre degeneration in hindlimb muscle as well as degeneration in sciatic nerve. Examination of brain samples from affected mice showed mild vacuolation in thalamus and in white matter areas, and atypical high intensity background immunohistochemical staining in white matter areas.
Western blotting, ELISA and immunohistochemistry studies did not detect PrPsc in brain samples from clinically affected Tg(BoPrP)2078 mice. This suggested that the spontaneous disease syndrome is due to prion protein (PrPc)-related disease, as a result of overexpression of transgenic bovine PrPc. Because of the apparent absence of PrPsc, this model is being assessed for susceptibility to BSE. Further studies will include investigation of the underlying pathological mechanisms in brain, and attempted transmission of the disease syndrome.
AD P.C.Griffiths, J.M.Plater, P.B.Rice, M.E.Field, O.J.Hazelby, S.S.J.Farrelly, O.Windl, TSE Molecular Biology Department, Veterinary Laboratories Agency (Weybridge), UK; R.E.Sallis, J.Spiropoulos, Neuropathology Unit, Veterinary Laboratories Agency (Weybridge), UK; L.Johnson, Histopathology Unit, Veterinary Laboratories Agency (Weybridge), UK
SP englisch
PO Deutschland