title: Ectopic expression of tmie transgene induces various recovery levels of behavior and hearing ability in the circling mouse.
abstract: The circling (cir/cir) mouse is one of the murine models for human non-syndromic deafness DFNB6. The mice have abnormal circling behavior, suggesting a balanced disorder and profound deafness. The causative gene was transmembrane inner ear (tmie) gene of which the mutation is a 40-kb genomic deletion including tmie gene itself. In this study, tmie-overexpression trasngenic mice were established. Individuals with germline transmission have been mated with circling homozygous mutant mice (cir/cir) in order to produce the transgenic mutant mice (cir/cir-tg) as a gene therapy. After the genotyping, phenotypic analyses were performed so that the insertion of the new gene might compensate for the diseases such as hearing loss, circling behavior, or swimming inability. Some individuals exhibited complete recovery in their behavior and hearing but the others did not show any amelioration in behavior or hearing. Individual mice had very different levels of tmie transgene expression in the cochlea. These results clearly indicate that tmie protein plays an important role when the appropriate expression level of tmie was expressed in the inner ear. The protein levels were variable in each individual and these are thought to induce the differences in disease amelioration levels.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea.
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Shin
authors.forename: Jeong-Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Yu
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Hei Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Channy
authors.initials: C
authors.lastname: Park
authors.forename: Byung-Hwa
authors.initials: BH
authors.lastname: Hyun
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005838:Genotype; D006198:Hair Cells, Auditory / Q000378:metabolism*; D006309:Hearing / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000628:therapy*; D006320:Hearing Tests; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D019076:Transgenes
chemical_list: D008565:Membrane Proteins; C530887:Tmie protein, mouse