This targeted mutation of the tectorin alpha (Tecta) gene displays partial to severe hearing loss and may be useful in studies of cochlear physiology and congenital hearing loss.
John S Oghalai, Baylor College of Medicine
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Humanized sequence) | Tecta | tectorin alpha |
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Heterozygous mice have a thickened and shortened tectorial membrane, which covers only the first of the three rows of the cochlear outer hair cells. In homozygotes the membrane is thicker, appears to be detached from the sensory epithelium, loosely connected to the spiral limbus and elevated from the organ of Corti. Heterozygous and homozygous mice exhibit, respectively, reduced and absent forward transduction, partial and severe hearing loss, partial and severe disruption of the fibrils surrounding the edges of the tectorial membrane. Both genotypes exhibit enhanced reverse transduction.
The targeting vector was designed to change the fourth von Willebrand Factor domain of the murine Tecta cDNA sequence (exons 13 and 14) from a cysteine to glycine at amino acid position 1509 (C1509G) of exon 14. An FRT-flanked neomycin cassette was inserted upstream of the coding sequence. The construct was electroporated into 129S7/SvEvBrd derived AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to 129S6/SvEv and the F1 progeny crossed to 129S4/SvJaeSor-Gt(ROSA)26Sortm1(FLP1)Dym/J to remove the neo cassette. Heterozygotes were crossed to CBA for five generations in the laboratory of the donating investigator. Upon arrival, mice were bred to CBA/J for at least 1 generation to establish the colony.
Allele Name | targeted mutation 1.1, John Oghalai |
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Allele Type | Targeted (Humanized sequence) |
Allele Synonym(s) | TectaC1509G |
Gene Symbol and Name | Tecta, tectorin alpha |
Gene Synonym(s) | |
Promoter | Tecta, tectorin alpha, mouse, laboratory |
Strain of Origin | 129S7/SvEvBrd-Hprtb-m2 |
Chromosome | 9 |
Molecular Note | Exon 14 was replaced with a modified one in which nucleotide substitution (T to G) resulted in the amino acid substitution of cysteine with glycine at position 1509 (p.C1509G). This mutation was identified in human patients with autosomal dominant hearing loss. A second silent nucleotide substitution (C to A) at codon for amino acid 1510 was generated to assist in genotypying. An FRT site flanked neomycin resistance gene cassette was inserted into intron 13 and was removed through subsequent flp-mediated recombination. |
Mutations Made By | John Oghalai, Baylor College of Medicine |
While maintaining a live colony, these mice are bred as heterozygotes or homozygotes.
When using the CBA.129S-Tectatm1.1Ogha/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010826 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Tecta<tm1Ogha> |
Frozen Mouse Embryo | CBA.129S-Tecta<tm1.1Ogha>/J | $2595.00 |
Frozen Mouse Embryo | CBA.129S-Tecta<tm1.1Ogha>/J | $2595.00 |
Frozen Mouse Embryo | CBA.129S-Tecta<tm1.1Ogha>/J | $3373.50 |
Frozen Mouse Embryo | CBA.129S-Tecta<tm1.1Ogha>/J | $3373.50 |
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