Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice

Sho Kanzaki, Lisa Beyer, I. Jill Karolyi, David F. Dolan, Qing Fang, Frank J. Probst, Sally A. Camper, Yehoash Raphael

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The shaker2 (sh2) mouse is a murine model for human non-syndromic deafness DFNB3. The mice have abnormal circling behavior suggesting a balanced disorder, and profound deafness. The insertion of a bacterial artificial chromosome (BAC) transgene containing the Myo15a gene into sh2/sh2 zygotes confers hearing capability and abolishes the circling behavior in 1-month-old transgenic animals. In this study, we investigated both the hearing and the morphology of the cochlea in Myo15a mutants carrying this BAC transgene at two, four, or six months of age. The hearing threshold of these mice is normal, with no physiologically significant differences compared to age-matched heterozygous sh2J mice (with or without the BAC transgene). In six-month-old transgenic mice with the BAC, the morphology of hair cells in the apical and upper basal turns of the cochlea is normal. Hair cells of lower basal turn, however, were missing in some mutant animals. This study demonstrates that BAC transgene correction cannot only maintain normal morphology but also confer stable hearing function in Myo15a mutant mice for as long as 6 months. In addition, excess Myo15a expression has no physiologically significant protective or deleterious effects on hearing of normal mice, suggesting that the dosage of Myo15a may not be problematic for gene therapy.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalHearing Research
Volume214
Issue number1-2
DOIs
Publication statusPublished - 2006 Apr

Fingerprint

Cochlea
Bacterial Artificial Chromosomes
Transgenes
Hearing
Deafness
Genetically Modified Animals
Zygote
Genetic Therapy
Transgenic Mice
Genes

Keywords

  • BAC transgene
  • Cytocaud
  • Phenotypic rescue
  • Shaker2 mouse

ASJC Scopus subject areas

  • Sensory Systems

Cite this

Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice. / Kanzaki, Sho; Beyer, Lisa; Karolyi, I. Jill; Dolan, David F.; Fang, Qing; Probst, Frank J.; Camper, Sally A.; Raphael, Yehoash.

In: Hearing Research, Vol. 214, No. 1-2, 04.2006, p. 37-44.

Research output: Contribution to journalArticle

Kanzaki, S, Beyer, L, Karolyi, IJ, Dolan, DF, Fang, Q, Probst, FJ, Camper, SA & Raphael, Y 2006, 'Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice', Hearing Research, vol. 214, no. 1-2, pp. 37-44. https://doi.org/10.1016/j.heares.2006.01.017
Kanzaki, Sho ; Beyer, Lisa ; Karolyi, I. Jill ; Dolan, David F. ; Fang, Qing ; Probst, Frank J. ; Camper, Sally A. ; Raphael, Yehoash. / Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice. In: Hearing Research. 2006 ; Vol. 214, No. 1-2. pp. 37-44.
@article{652d58f03aa24fc99acd51a07bf8e884,
title = "Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice",
abstract = "The shaker2 (sh2) mouse is a murine model for human non-syndromic deafness DFNB3. The mice have abnormal circling behavior suggesting a balanced disorder, and profound deafness. The insertion of a bacterial artificial chromosome (BAC) transgene containing the Myo15a gene into sh2/sh2 zygotes confers hearing capability and abolishes the circling behavior in 1-month-old transgenic animals. In this study, we investigated both the hearing and the morphology of the cochlea in Myo15a mutants carrying this BAC transgene at two, four, or six months of age. The hearing threshold of these mice is normal, with no physiologically significant differences compared to age-matched heterozygous sh2J mice (with or without the BAC transgene). In six-month-old transgenic mice with the BAC, the morphology of hair cells in the apical and upper basal turns of the cochlea is normal. Hair cells of lower basal turn, however, were missing in some mutant animals. This study demonstrates that BAC transgene correction cannot only maintain normal morphology but also confer stable hearing function in Myo15a mutant mice for as long as 6 months. In addition, excess Myo15a expression has no physiologically significant protective or deleterious effects on hearing of normal mice, suggesting that the dosage of Myo15a may not be problematic for gene therapy.",
keywords = "BAC transgene, Cytocaud, Phenotypic rescue, Shaker2 mouse",
author = "Sho Kanzaki and Lisa Beyer and Karolyi, {I. Jill} and Dolan, {David F.} and Qing Fang and Probst, {Frank J.} and Camper, {Sally A.} and Yehoash Raphael",
year = "2006",
month = "4",
doi = "10.1016/j.heares.2006.01.017",
language = "English",
volume = "214",
pages = "37--44",
journal = "Hearing Research",
issn = "0378-5955",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice

AU - Kanzaki, Sho

AU - Beyer, Lisa

AU - Karolyi, I. Jill

AU - Dolan, David F.

AU - Fang, Qing

AU - Probst, Frank J.

AU - Camper, Sally A.

AU - Raphael, Yehoash

PY - 2006/4

Y1 - 2006/4

N2 - The shaker2 (sh2) mouse is a murine model for human non-syndromic deafness DFNB3. The mice have abnormal circling behavior suggesting a balanced disorder, and profound deafness. The insertion of a bacterial artificial chromosome (BAC) transgene containing the Myo15a gene into sh2/sh2 zygotes confers hearing capability and abolishes the circling behavior in 1-month-old transgenic animals. In this study, we investigated both the hearing and the morphology of the cochlea in Myo15a mutants carrying this BAC transgene at two, four, or six months of age. The hearing threshold of these mice is normal, with no physiologically significant differences compared to age-matched heterozygous sh2J mice (with or without the BAC transgene). In six-month-old transgenic mice with the BAC, the morphology of hair cells in the apical and upper basal turns of the cochlea is normal. Hair cells of lower basal turn, however, were missing in some mutant animals. This study demonstrates that BAC transgene correction cannot only maintain normal morphology but also confer stable hearing function in Myo15a mutant mice for as long as 6 months. In addition, excess Myo15a expression has no physiologically significant protective or deleterious effects on hearing of normal mice, suggesting that the dosage of Myo15a may not be problematic for gene therapy.

AB - The shaker2 (sh2) mouse is a murine model for human non-syndromic deafness DFNB3. The mice have abnormal circling behavior suggesting a balanced disorder, and profound deafness. The insertion of a bacterial artificial chromosome (BAC) transgene containing the Myo15a gene into sh2/sh2 zygotes confers hearing capability and abolishes the circling behavior in 1-month-old transgenic animals. In this study, we investigated both the hearing and the morphology of the cochlea in Myo15a mutants carrying this BAC transgene at two, four, or six months of age. The hearing threshold of these mice is normal, with no physiologically significant differences compared to age-matched heterozygous sh2J mice (with or without the BAC transgene). In six-month-old transgenic mice with the BAC, the morphology of hair cells in the apical and upper basal turns of the cochlea is normal. Hair cells of lower basal turn, however, were missing in some mutant animals. This study demonstrates that BAC transgene correction cannot only maintain normal morphology but also confer stable hearing function in Myo15a mutant mice for as long as 6 months. In addition, excess Myo15a expression has no physiologically significant protective or deleterious effects on hearing of normal mice, suggesting that the dosage of Myo15a may not be problematic for gene therapy.

KW - BAC transgene

KW - Cytocaud

KW - Phenotypic rescue

KW - Shaker2 mouse

UR - http://www.scopus.com/inward/record.url?scp=33646023151&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646023151&partnerID=8YFLogxK

U2 - 10.1016/j.heares.2006.01.017

DO - 10.1016/j.heares.2006.01.017

M3 - Article

C2 - 16580798

AN - SCOPUS:33646023151

VL - 214

SP - 37

EP - 44

JO - Hearing Research

JF - Hearing Research

SN - 0378-5955

IS - 1-2

ER -