Retroviral spongiform degenerative disease produced by the murine neurotropic retrovirus Cas-Br-E.
The murine neurotropic retrovirus Cas-Br-E causes a non-inflammatory spongiform neurodegenerative disease involving the spinal cord, brainstem and cerebellum, manifest as a progressive, fatal lower motor neuron disease. Using in utero infection of mid-gestation mouse embryos, we have developed a rapid model for the study of this disease. Infection of mid-gestation embryos caused paralysis and death within 25 days after birth, in contrast to virus-infected neonates, which develop disease only after three months. We have found that this model is well suited not only to the study of neurovirulence but also to the rapid, quantitative assessment of treatment strategies in the CNS. The drug 3'-azido-3'-deoxythymidine (AZT) was found to cross the placental barrier effectively and markedly retarded the onset and course of disease, when given to infected embryos through the drinking water of pregnant females. CNS injury seems to be due to a direct viral action, but the precise target cells of the virus are uncertain. The identification of the viral target cells is complicated by the presence of numerous endogenous retroviruses in the mouse genome, as well as difficulties with identifying infected cell types by morphology alone. To identify Cas-Br-E-infected cells precisely, we have performed in situ hybridization studies using a Cas-Br-E-specific riboprobe and found that infected cells are in regions of the CNS in which spongiform lesions develop and in regions without any obvious pathology.(ABSTRACT TRUNCATED AT 250 WORDS)
Sharpe
A H
AH
Department of Pathology, Harvard Medical School, Boston, MA.
Jaenisch
R
R
D000818:Animals; D000835:Animals, Wild / Q000382:microbiology; D002490:Central Nervous System / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000188:drug therapy / Q000382:microbiology; D017988:Gammaretrovirus / Q000302:isolation & purification / Q000472:pathogenicity*; D005865:Gestational Age; D017403:In Situ Hybridization; D051379:Mice / Q000382:microbiology*; D008845:Microinjections; D016472:Motor Neuron Disease / Q000188:drug therapy / Q000382:microbiology*; D011247:Pregnancy; D012192:Retroviridae Infections / Q000188:drug therapy / Q000382:microbiology* / Q000635:transmission; D012376:Rodent Diseases / Q000188:drug therapy / Q000382:microbiology* / Q000635:transmission; D015215:Zidovudine / Q000627:therapeutic use
D015215:Zidovudine