Tg[E] BAC transgenic mice are viable and fertile, with a reverse tetracycline-regulated transactivator 2 (rtTA2) gene and a neo cassette, in reverse orientation, replacing the start codon of the solute carrier family 26, member 4 (Slc26a4 or Pendrin) gene on the BAC transgene. Pendrin is sodium-independent transporter of chloride and iodide expressed in inner ear, thyroid, kidney, and subset of other organs. Mutations in Pendrin have been associated with the onset of Pendred syndrome, a common form of syndromic autosomal-recessive deafness. Pendrin KO mice exhibit severe developmental abnormalities starting with enlargement of the endolymphatic sac and cochlea beginning at E14.5, cochlear endolymph acidification at E15.5, developmental retardation of the stria vascularis at P3, loss of the endocochlear potential at P10, degeneration of hair cells as early as P15, and failure to acquire hearing between P12 and P15. When mated to a second transgenic strain carrying a gene of interest under the regulatory control of a tetracycline-responsive promoter element (tetO), expression of the target gene may be regulated by the tetracycline analog, doxycycline (dox). In the presence of dox, transcription of the target gene is induced in cells where rtTA is expressed. Hemizygous Tg[E] transgenic mice are viable and fertile.
When bred to a strain expressing Slc26a4 under control of the tetO promoter (Stock No. 028681), double transgenic mice on a Slc26a4-null background (Stock No. 018424) show differential effects on the severity of hearing loss by varying the temporal expression of Pendrin.
