B6;129S-Barhl1^tm1Xia/J

Stock number: 013193
Research areas: Dermatology Research, Neurobiology Research, Sensorineural Research

Description

In this strain, the entire coding region of the endogenous BarH-like 1 (Barhl1) gene is replaced with a lacZ (β-galactosidase) reporter gene, and a loxP-flanked neomycin resistance (neo) cassette, abolishing gene function. These Barhl1^-/- mutant mice may be useful as a lacZ reporter for BARHL1 expression, and for studying age-related human deafness disorders.

Detailed description

In this strain, the entire coding region of the endogenous BarH-like 1 (Barhl1) gene is replaced with a lacZ (β-galactosidase) reporter gene and a loxP-flanked neomycin resistance (neo) cassette, abolishing gene function. Homozygous mice are viable, fertile, and normal in size, with β-gal staining in Barhl1 expressing tissues. LacZ expression in embryos and neonates is evident in all hair cells, but is more abundantly observed in the cochlear outer hair cells. LacZ expression in adults is strong in the outer hair cells, and weak in the inner and vestibular hair cells, with persistent expression in hair cells of the organ of Corti. These mice exhibit age-related progressive degeneration of both cochlear outer and cochlear inner hair cells in the organ of Corti, resulting in hearing loss. The progression is apical-to-basal for outer hair cell and basal-to-apical for inner hair cells. Barhl1^-/- mice have elevated auditory brainstem response (ABR) thresholds at all frequencies tested while some did not respond to any auditory stimuli. 2 week old Barhl1^-/- mice have a reduced startle reflex and exhibit a loss of low-frequency hearing, while 3 month old mutants lose high-frequency hearing. By 6 months of age the mutants exhibit near complete loss of outer hair cells, with complete loss by 10 months, rendering the mice deaf. These Barhl1^-/- mutant mice may be useful as a lacZ reporter for BARHL1 expression, and for studying age-related human deafness disorders.

Development

A targeting vector was designed to replace the entire coding region of the BarH-like 1 (Barhl1) gene with a lacZ (β-galactosidase) reporter gene, and a loxP-flanked neomycin resistance (neo) cassette. The construct was electroporated into 129S7/SvEvBrd-Hprt1^b-m2-derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to C57BL/6J mice to generate a colony of Barhl1^-/- mice. These mice were maintained on a mixed background. Upon arrival at The Jackson Laboratory, mice were bred to B6129SF1/J (Stock No. 101043) for at least one generation to establish the colony.

Allele

Symbol: Barhl1^tm1Xia
Name: targeted mutation 1, Mengqing Xiang
MGI accession ID: MGI:2181383
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Barhl1
Marker name: BarH like homeobox 1
Chromosome: 2
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
Expressed genes: lacZ,beta-galactosidase,E. coli
Molecular note: The coding region of the gene was replaced with a lacZ/PGK-neo casette. The PGK-neo portion of the cassette is flanked by loxP sites.