B6;CBA-Tg(Mpz-RAF1/ESR1)A668Ayld/J

Stock number: 018449
Research areas: Apoptosis Research, Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research

Description

P₀-RafTR mice transgenic mice can be used to conditionally activate the ERK pathway is Schwann cells. They may have applications in studies related to cancer and peripheral neuropathies.

Detailed description

P₀-RafTR mice express the kinase domain of human c-raf-leukemia viral oncogene 1 (Raf Kinase, Raf1)/ER (a tamoxifen inducible human estrogen receptor ligand binding domain) fusion gene under the direction of a modified rat myelin protein zero (Mpz) promoter. Expression of the fusion gene is observed in myelinating Schwann cells. P₀ is a glycoprotein located in Schwann cells of the peripheral nervous system. Schwann cells are important for regeneration and restoration of nerve function after injury. Demyelination of Schwann cells has been associated with peripheral neuropathies, neurofibromas, and fibrosarcomas. Tamoxifen administration in carrier mice results in the activation of the RAF kinase-fusion protein in myelinating Schwann cells, followed by severe demyelination within the peripheral nervous system that results in ataxia and impaired motor function. Mice exhibit many of the inflammatory responses important for nerve repair including permeability of the blood nerve barrier and recruitment of macrophages and other inflammatory cells. This phenotype is dose-dependent and reversible upon withdrawal of tamoxifen. Axonal fibers in these mice remain structurally unaffected.

Development

A v-raf-leukemia viral oncogene 1 (Raf Kinase, Raf1)/ER (a tamoxifen inducible human estrogen receptor ligand binding domain) fusion gene was placed under the control of the rat myelin protein zero (Mpz) promoter. This transgenic construct was introduced into C57BL/6J donor oocytes and resulting offspring from founder line A668 were bred to B6CBAF1/J mice. These mice were subsequently bred to B6CBAF1/J mice every generation. Upon arrival at The Jackson Laboratory, mice were bred to B6CBAF1/J mice (Stock No. 100011) to establish the colony.

Allele

Symbol: Tg(Mpz-RAF1/ESR1)A668Ayld
Name: transgene insertion A668, Alison Lloyd
MGI accession ID: MGI:5427464
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence
Marker symbol: Tg(Mpz-RAF1/ESR1)A668Ayld
Marker name: transgene insertion A668, Alison Lloyd
Chromosome: UN
Strain of origin: C57BL/6J
Expressed genes: RAF1,Raf-1 proto-oncogene, serine/threonine kinase,human; ESR1,estrogen receptor 1,human
Molecular note: A v-raf-leukemia viral oncogene 1 (Raf Kinase, Raf1)/ER (a tamoxifen-inducible human estrogen receptor ligand-binding domain) fusion gene was placed under the control of the rat myelin protein zero (Mpz) promoter. Line 668 was generated.