C57BL/6J-Actb^em1Erv/J

Stock number: 032628
Product name: Actb^c-g
Research areas: Neurobiology Research, Sensorineural Research

Description

Actb^c-g knock-in/knock-out (KI/KO) mice are altered to encode the Actg1 (actin, gamma, cytoplasmic 1) gene and retain all the endogenous Actb (actin, beta) regulatory elements. Homozygous mice exhibit progressive high-frequency hearing loss and degeneration of actin-based stereocilia. This strain may be useful for studying functional differences between beta and gamma actin.

Detailed description

Actb (beta actin) is one of 6 actin isoforms involved in cell motility, structure, integrity, and intercellular signaling. Two of the actin isoforms, beta and gamma, are specific to the cytoplasm and differ by 4 out 375 amino acids. Point mutations in both Actb and Actg1 are associated with developmental defects and progressive hearing loss. In these Actb^c-g knock-in/knock-out (KI/KO) mice, TALEN genome editing is used to alter the Actb gene to encode Actg1 and retain all the endogenous Actb regulatory elements. Actb^c-g mice are null for the beta-actin protein. Mice homozygous for the mutation are viable and fertile with no obvious phenotype. Of note, Actb KO mice are normally embryonic lethal. Beginning at 6 weeks of age, Actb^c-g mice develop progressive high-frequency (32 kHz) hearing loss. By 6 months of age, actin-based stereocilia have begun to degenerate and are shorter and fewer in number than controls. Outer hair cells stereocilia bundles are missing in some mice. This strain may be useful for studying functional differences between beta and gamma actin.

Development

TALEN-based genome editing was used to introduce 8 nucleotide alterations, which function to exchange the translation of beta-actin D2-4, V10 to gamma-actin E2-4, I10, and to disrupt TALEN re-binding to the edited locus. TALEN mRNAs were introduced by pronuclear injection into C57BL/6 blastocysts. Offspring were crossed to C57BL/6J and maintained on C57BL/6J. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Actb^em1Erv
Name: endonuclease-mediated mutation 1, James Ervasti
MGI accession ID: MGI:6209780
Generation method: Endonuclease-mediated
Attributes: Null/Knockout
Synonyms: Actb^c-g
Marker symbol: Actb
Marker name: actin, beta
Marker synonyms: Actx; A-X actin-like protein; beta-actin; BKRNS; BNS; BRWS1; CSMH; DDS1; E430023M04Rik; PS1TP5BP1; THC8
Chromosome: 5
Strain of origin: C57BL/6
Molecular note: TALEN-based genome editing was used to introduce 8 nucleotide alterations, which function to exchange the translation of beta-actin D2-4, V10 to gamma-actin E2-4, I10, and to disrupt TALEN re-binding to the edited locus. Mice are null for the beta-actin protein.