A neo cassette replaces exon 8 of the solute carrier family 26, member 4 (Slc26a4) gene abolishing gene expression in these Pds-/- mutant mice. A truncated transcript containing part of the neo cassette is detected in kidney RNA. Homozygotes are viable and fertile, but females often cannibalize their litters. The Slc26a4 gene product, pendrin, is an anion transporter expressed in epithelial cells of the thyroid, inner ear, and kidney. Pendrin mutations are associated with an enlarged vestibular aqueduct and Pendred syndrome (PS). Profound deafness is observed in both situations. Symptoms of PS also include an abnormal thyroid phenotype resulting in hypothyroidism and goiters. These Pds-/- mice are completely deaf. They have normal inner ear morphology until E15 when endolymphatic dilation occurs as seen in PS. During the second week after birth, abnormal inner ear morphology is evident, including degeneration of sensory cells, malformation of otoconia and otoconial membranes, and abnormally enlarged cochlear lumen. Half of homozygotes show signs of vestibular dysfunction, including circling, head-tilting, head-bobbing and abnormal reaching responses. Mice have a mild inability to alkalinize urine and notably, have a normal thyroid phenotype.
A targeting vector was designed to replace exon 8 of the solute carrier family 26, member 4 (Slc26a4) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to 129Sv/Ev females. These mice were bred together to generate a colony of Pds-/- mice. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ mice (Stock No. 002448) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Eric D Green|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Pds-; Slc26a4delta|
|Gene Symbol and Name||Slc26a4, solute carrier family 26, member 4|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Exon 8 was replaced with a neomycin selection cassette via homologous recombination. While, normal transcript was undetected by RT-PCR and Northern blot analyses of total kidney RNA isolated from homozygous mutant mice, RT-PCR revealed the presence of an aberrant transcript containing a portion of the neo cassette.|
|Mutations Made By|| |
Eric Green, National Human Genome Research Institute
When maintaining a live colony, heterozygous females may be bred to homozygous males. The donating investigator reports that homozygous females often cannibalize their litters
When using the 129S-Slc26a4tm1Egr/AjgJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #018424 in your Materials and Methods section.