These mice carry an ENU-induced mutation characterized by abnormal ear development and deafness.
The Jackson Laboratory cannot guarantee that cryorecovery of strains from the discontinued NIH-funded Neuroscience Mutagenesis Facility (NMF) will be successful or that the anticipated phenotype or genotype will be obtained. The cryorecovery fee for this effort will not be refunded or prorated if the recovery is unsuccessful or is in any way unsatisfactory. Genotyping will be the responsibility of the Purchaser.
Read More +Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Chemically induced (ENU) (Hypomorph) | Tbx1 | T-box 1 |
The highly conserved TBX1 transcription factor is essential for normal development and mutations are associated with conotruncal anomaly face syndrome, DiGeorge syndrome, tetralogy of Fallot, and velocardiofacial syndrome. Tbx1 homozygous null mutant mice die neonatally with truncas arteriosis and other cardiac developmental defects, cleft palate and other craniofacial defects, thymic defects, otic vesicle hypoplasia and other ear defects, and other defects stemming from defective development of the pharyngeal pouches. Mice heterozygous for null alleles have also been found to have abnormal aortic arch morphology and some neonatal lethality. The nmf219 point mutation in Tbx1 is not a null allele but rather a single amino acid substitution of glycine in place of aspartic acid at amino acid 212 in the T-Box DNA binding domain. TBX1 protein expression is found in homozygotes and appears reasonably similar to that of wildtype controls by immunohistochemistry of P3 and P15 inner ears. This substitution does not cause homozygous lethality or the severe cardiovascular, thymic and craniofacial defects that other Tbx1 mutations cause, but still causes developmental defects of the stria vascularis and semicircular canals, resulting in complete deafness and the circling and head tossing phenotypes indicative of a vestibular defect. Homozygotes as young as 4 weeks of age displayed no detectable ABR at 100 dB SPL at 8, 16, or 32 kHz.
The underlying developmental failure stems in part from the failure of epithelial cells to become mature marginal cells such that at P3 there are few or no marginal cells interdigitating with intermediate cells at the stria vascularis. This may result from failure of mutant TBX1 to induce expression of Esrrb in the inner ear, which is diminished compared with controls at E16.5 and P3. At the earliest timepoint assessed, E14.5, defects are found and paintfills of inner ears at E14.5 and E16.5 found that there is a single fused ampulla connecting the anterior and lateral canals, the fusion plate of the posterior semicircular canal fails to resorb, the posterior canal ampulla is not formed, and the posterior semicircular canal is fused with the common crus. As a result, at 7 days of age the stria vascularis is underdeveloped, the scala media small, and Reissner’s membrane is displaced, and at 5 months of age the stria vascularis is still severely underdeveloped, the scala media extremely reduced, Reissner’s membrane is collapsed, there is degeneration of the organ of Corti and loss of spiral ganglion neurons. in situ hybridization and RNA-Seq have identified an array of transcripts with upregulated or downregulated expression relative to controls. (Tian and Johnson, 2019.)
This phenotypic deviant was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males (Stock No. 000664), in the Neuroscience Mutagenesis facility at The Jackson Laboratory. Mutagenized males were crossed to C57BL/6J females; G3 descendants of the mutagenized males were selected for neurological impairment.
Allele Name | neuroscience mutagenesis facility, 219 |
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Allele Type | Chemically induced (ENU) (Hypomorph) |
Allele Synonym(s) | nmf219 |
Gene Symbol and Name | Tbx1, T-box 1 |
Gene Synonym(s) | |
Strain of Origin | C57BL/6J |
Chromosome | 16 |
Molecular Note | This ENU-induced A to G point substitution at coding position 653 results in the replacement of aspartic acid with glycine at amino acid 212, which is a highly conserved residue in the T-Box DNA binding domain. |
Homozygous females breed, but their circling phenotype may make them poor mothers.
When using the C57BL/6J-Tbx1nmf219/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004831 in your Materials and Methods section.
Facility Barrier Level Descriptions
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Unknown for nmf219 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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