The pBi-Noggin-eGFP transgene has a bidirectional tetracycline-inducible promoter controlling expression of noggin and eGFP. No transgenic noggin or eGFP expression is reported in the absence of tetracycline-controlled transactivator protein (tTA). When bred to other mice expressing tTA or reverse tetracycline-controlled transactivator protein (rtTA), simultaneous noggin and eGFP expression in the resulting double mutant offspring can be regulated by tetracycline or its analog doxycycline (dox). Mice from founder line 53 were found to have the highest and most stable expression of transgenic noggin and eGFP after dox administration, with the lowest background expression levels. When induced, eGFP expression is readily observed via immunohistochemical detection, but direct eGFP fluorescence is very faint. FVB.pBi-Noggin-eGFP line 53 hemizygotes are viable and fertile, with no reported phenotypic abnormalities. The transgene integration site and copy number analysis is summarized below. The donating investigator reports that homozygous mice are viable and fertile, with behavior and gene expression the same as hemizygous animals. When FVB.pBi-Noggin-eGFP line 53 mice are bred to mice expressing rtTA in central nervous system (Nestin-rtTA; see Stock No. <a href="https://www.jax.org/strain/004127">004127</a>), the resulting double mutant offspring may be useful in mobilizing endogenous neural stem cell populations to replace neurons and oligodendrocytes lost as a result of disease, injury, and normal or pathological aging. Immunohistochemical localization of nestin and eGFP in sections of doxycycline-induced brain also showed complete overlap. In the absence of doxycycline, noggin over-expression is not observed. 
 Note on transgene insertion and copy number: In 2017, the pBi-Noggin-eGFP colony at The Jackson Laboratory was screened to determine the transgene integration site(s). This analysis revealed two transgene integration sites in a complex manner (including one transgene-transgene fusion event) - both within the Golgb1 locus on chromosome 16. This also resulted in two duplications of Golgb1 genome region (totaling ~22.3 kb) fused to transgene sequences. The number of transgene copies at each site was not determined. The transgene insertion effect on Golgb1 expression has not been specifically determined to date [April 2022].

These pBi-Noggin-eGFP transgenic mice allow Tet-inducible inhibition of transforming growth factor (TGF)-beta signal transduction (including bone morphogenetic protein (BMP)-signaling pathway), and may be useful in studying these signaling pathways during embryonic development, in postnatal tissues, and in sites of adult neurogenesis. These animals may also be used for mobilizing endogenous neural stem cell populations to replace neurons and oligodendrocytes lost as a result of disease, injury, and normal or pathological aging.
 Please note, the transgene has integrated within the Golgb1 locus - see Detailed Description section for details.

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