Young Scientist Award Secondary Examination Developmental Engineering Breeding / Strain Development Management / Welfare Mitochondria Virus Bacteria Gene Function QTL Analysis Bioresource and Database Animal Models for Human Disease Neuroscience / Behavior Cancer Immunology Pathogenic Analysis Fertilization / Early Development
Аннотация:Chronic hepatitis C, caused by infection with hepatitis C virus (HCV), is a global health problem; however, no effective therapy for patients with chronic infection has yet been developed.To address how HCV infection causes chronic liver diseases and design an effective HCV vaccine, we generated immunocompetent mice expressing HCV structural proteins through the Cre/loxP switching system and established an attenuated recombinant vaccinia virus strain, rVV-N25.At 7 days after intradermal injection, rVV-N25 immunization suppressed the serum inflammatory cytokine levels and thereby cured chronic hepatitis C symptoms (steatosis etc.) irrespective of viral protein clearance.Furthermore, at 2-days after rVV-N25 immunization, the HCV protein levels in the liver tissues decreased in a CD4 and CD-T-cell-dependent manner.We also demonstrated that the pathogenesis of chronic hepatitis C is mainly attributable to inflammatory cytokines (TNF-alpha and IL-6).These results provide a basis for developing an effective therapeutic vaccine against HCV.Differences of hearing have been reported among mouse inbred strains.The genetic factor, associated with these differences of hearing, would be useful information for identification of responsible genes in human deafness.To identify the association between hearing and genetic background, we investigated auditory brainstem response (ABR) thresholds to tone-pip 4-, 8-, 16-, and 32 kHz stimuli in C3H, B6, BALB, D2, NOD, JF1 and M-M inbred strains.C-H and M-M showed normal hearing until 12 and 1-month-of-age, respectively.On the other hand, B6 and BALB showed hearing loss in 9 month-of-age.This age-related hearing loss was caused by a mutation in cadherin 2-encoding gene (Cdh23 ahl1 ).Whereas, D2 and NOD, which has Cdh23 ahl1 same as B6, already showed the hearing loss at one month-of age due to a missense mutation of Fscn2 gene and ahl2 locus respectively.Moreover, the heterozygousity of Walzter (Cdh23 v ) or Jackson shaker (Sans js ) mutant allele showed the early-onset of deafness in B6 background.This early-onset hearing loss might be caused by an interaction between Cdh23 ahl1 and Cdh23 v /Sans js .Although JF1 showed congenital hearing loss, normal hearing was shown in JF1-revartant strain.This result might be caused by normal expression of Ednrb transcripts.
Год издания:2011
Источник:EXPERIMENTAL ANIMALS
Ключевые слова:Animal Genetics and Reproduction, Birth, Development, and Health
