Endocrine Abstracts

Interspecies transmission of prion diseases both centrally and peripherally is associated with longer incubation periods and lower effective titres to within species transmission, a phenomenon called the 'species barrier'. Research into interspecies transmission and disease pathogenesis is crucial for understanding disease risk for vCJD, which has been persistently linked to BSE. Host genetics, transmission route and strain of infective agent have generally been shown to affect disease course and neuropathology. We have used 2 BXD inbred mouse strains and their progenitor to investigate host adaptation of BSE. Following anaesthesia, a primary isolate of BSE or its secondary form was intracerebrally administered to both sexes of the 4 strains of mice. Mice were observed for onset of clinical BSE by standard procedures and diagnoses were confirmed by neuropathology.

Results show that in primary transmission incubation periods in days (Mean plus/minus SEM) were longer in females [BXD 6ty = 516 plus/minus 11; BXD 21ty = 274 plus/minus 20; DBA = 278 plus/minus 3; C57BL/6J = 454 plus/minus 16] compared to males [BXD 6ty = 216 plus/minus 18; BXD 21ty = 158 plus/minus 13; DBA = 185 plus/minus 10; C57BL/6J = 174 plus/minus 5] in all strains. However, there is no difference between sexes with secondary transmission in all the strains: for females, BXD 6ty = 93 plus/minus 15; BXD 21ty = 103 plus/minus 1; DBA = 112 plus/minus 2; C57BL/6J = 120 plus/minus 3; for males, BXD 6ty = 111 plus/minus 6; BXD 21ty = 99 plus/minus 12; DBA = 91 plus/minus 11; C57BL/6J = 133 plus/minus 1.

This strongly suggests that sex-specific factors are involved in host adaptation of BSE and may have implications for devising therapy for vCJD.