C57BL/6-Myo3a^tm1.1Mckg/J

Stock number: 014165
Research areas: Mouse/Human Gene Homologs, Sensorineural Research

Description

These Myo3a^KI/KI mice contain the nonsense mutation TAT>TAG at codon 1041 of the myosin IIIA gene. This mutation introduces a premature stop codon in exon 28, analogous to a Myo3a mutation found in humans with adult on-set hearing loss (DFNB30). These mice may be useful for studying adult on-set human hearing loss DFNB30.

Detailed description

These Myo3a^KI/KI mice contain the nonsense mutation TAT>TAG at codon 1041 of the myosin IIIA (Myo3a) gene. This mutation introduces a premature stop codon in exon 28, analogous to a Myo3a mutation found in humans with adult on-set hearing loss (DFNB30). Homozygotes are viable, fertile, and normal in size. DFNB30 is an inherited progressive hearing loss first identified in a Middle Eastern family, Family N. Myo3a is normally expressed in the vestibular hair cells of the inner ear. These mice exhibit significant hearing loss during the third month of life, beginning at high frequencies and eventually progressing to all frequencies. The inner and outer hair cells of these mice exhibit degeneration by 10 and 17 months of age, respectively, showing greater loss towards the base of the cochlea. These mice may be useful for studying adult on-set human hearing loss DFNB30.

Development

A targeting construct was designed to insert the nonsense mutation TAT>TAG at codon 1041 of the myosin IIIA (Myo3a) gene. This mutation, corresponding to human codon 1042, results in a stop codon in exon 28 commonly found in humans with adult on-set hearing loss DFNB30. Also, an ACN cassette was placed upstream of exon 28. The ACN cassette, containing the neomycin resistance gene and Cre recombinase gene under the control of angiotensin-converting enzyme promoter, is flanked by loxP sites. Cre-mediated recombination during spermatogenesis removed the cassette leaving one loxP site. This construct was electroporated into C57BL/6-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into BALB/c blastocysts. The resulting chimeric mice were bred to C57BL/6 mice to produce Myo3a^KI/KI mice. Cryopreserved embryos were sent to The Jackson Laboratory Repository. Upon arrival, mutant mice were bred together (or to C57BL/6J (Stock No. 000664) mice for at least one generation) to establish the colony.

Allele

Symbol: Myo3a^tm1.1Mckg
Name: targeted mutation 1.1, Mary-Claire King
MGI accession ID: MGI:4849286
Generation method: Targeted
Attributes: Humanized sequence
Synonyms: Myo3a^KI
Marker symbol: Myo3a
Marker name: myosin IIIA
Marker synonyms: 9030416P08Rik; DFNA90; DFNB30
Chromosome: 2
Strain of origin: C57BL/6
Molecular note: A targeting construct was designed to insert the nonsense mutation TAT>TAG at codon 1041 of the myosin IIIA (Myo3a) gene. This mutation, corresponding to human codon 1042, results in a stop codon in exon 28 commonly found in humans with adult on-set hearing loss DFNB30. Also, an ACN cassette was placed upstream of exon 28. The ACN cassette, containing the neomycin resistance gene and Cre recombinase gene under the control of angiotensin-converting enzyme promoter, is flanked by loxP sites. Cre-mediated recombination during spermatogenesis removed the cassette leaving one loxP site.