B6;SJL-Tg(tetO-Egfr*)2-9Jek/J

Stock number: 010575
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

These TetRE-EGFR-tr (TRE-EGFR-tr) transgenic mice express a dominant negative, cytoplasmic tyrosine kinase domain-deleted mutant form of epidermal growth factor receptor (EGFR-tr) regulated by the tetracycline operator (tetO; also called tetracycline-responsive element (TRE, TetRE) or tet-operator) and cytomegalovirus minimal promoter. EGFR-tr expression disrupts subsequent activation of signal transduction pathways that are involved in regulating cellular proliferation, differentiation, and survival. These TetRE-EGFR-tr mice may be bred to generate bi-transgenic mutant mice with conditional (inducible/reversible) expression of a dominant negative EGF receptor, and may be useful in studying receptor tyrosine kinase function of the EGF receptor (ErbB) family proteins and their extracellular protein ligands (including EGF, TGF-α and neuregulins).

Detailed description

The donating investigator reports that homozygous mice are viable and fertile. These TetRE-EGFR-tr (TRE-EGFR-tr) transgenic mice express a dominant negative, cytoplasmic tyrosine kinase domain-deleted mutant form of epidermal growth factor receptor (EGFR-tr) regulated by the tetracycline operator (tetO; also called tetracycline-responsive element (TRE, TetRE) or tet-operator) and cytomegalovirus minimal promoter. When mated to a mutant strain expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA), tissue EGFR-tr expression may be regulated with the tetracycline analog doxycycline (dox) in the double mutant offspring. EGFR-tr expression disrupts subsequent activation of signal transduction pathways that are involved in regulating cellular proliferation, differentiation, and survival. These TetRE-EGFR-tr mice may be bred to generate bi-transgenic mutant mice with conditional (inducible/reversible) expression of a dominant negative EGF receptor, and may be useful in studying receptor tyrosine kinase function of the EGF receptor (ErbB) family proteins and their extracellular protein ligands (including EGF, TGF-α and neuregulins).

For example, when bred to a strain expressing rtTA in pituitary somatotropes (see Stock No. 010574), this mutant mouse strain may be useful in studies of pituitary development.

When bred to a strain expressing tTA in pituitary lactotropes/mammotropes (see Stock No. 010573 for example), this mutant mouse strain may be useful in studies of pituitary development.

Development

The TetRE-EGFRtr-SV40 transgene was designed with the tetracycline operator (tetO; also called tetracycline-responsive element (TRE, TetRE) or tet-operator) and cytomegalovirus minimal promoter, a 2.3 kb C-terminal truncated mouse epidermal growth factor receptor cDNA sequence (EGFR-tr; encoding amino acid 1-690 followed by a TGA stop codon), and an SV40 intron/polyA sequence. This 4.5 kb transgene was microinjected into one-cell (C57BL/6 x SJL) mouse zygotes. Mice from founder line 2-9 were bred with C57BL/6;SJL wildtype mice to establish the colony. The donating investigator reports that TetRE-EGFR-tr transgenic mice were bred with rtTA-transgenic mice (on the same mixed C57BL/6;SJL genetic background), and then together or to wildtype siblings for many generations. Mice harboring only the TetRE-EGFR-tr transgene were then sent to The Jackson Laboratory. Upon arrival, transgenic mice were bred with B6SJLF1/J hybrid mice (Stock No. 100012) for at least one generation to establish this colony.

Allele

Symbol: Tg(tetO-Egfr*)2-9Jek
Name: transgene insertion 2-9, Jeffrey E Kudlow
MGI accession ID: MGI:3850383
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence
Marker symbol: Tg(tetO-Egfr*)2-9Jek
Marker name: transgene insertion 2-9, Jeffrey E Kudlow
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)
Expressed genes: Egfr,epidermal growth factor receptor,mouse, laboratory
Molecular note: The TetRE-EGFRtr-SV40 transgene was designed with the tetracycline operator (tetO; also called tetracycline-responsive element (TRE, TetRE) or tet-operator) and cytomegalovirus minimal promoter, a 2.3 kb C-terminal truncated mouse epidermal growth factor receptor cDNA sequence (EGFR-tr; encoding amino acid 1-690 followed by a TGA stop codon), and an SV40 intron/polyA sequence. This 4.5 kb transgene was microinjected into one-cell (C57BL/6 x SJL) mouse zygotes. Mice from founder lines 2-9 were bred with C57BL/6;SJL wildtype mice to establish the colony.