C.B6-Tg(Fap-TK)MRkl/J

Stock number: 035907
Product name: FAP-TK
Research areas: Cancer Research, Research Tools

Description

FAP-TK transgenic mice express an inducible suicide gene, Herpes simplex virus thymidine kinase (TK), in carcinoma-associated fibroblasts. Administration of ganciclovir results in the ablation of FAP⁺ (fibroblast activation protein) cells. These mice may be useful for the study of pancreatic ductal adenocarcinoma (PDAC).

FAP-TK transgenic mice are available on the BALB/c (this strain - Stock No. 035907) and C57BL/6J (Stock No. 034655) backgrounds.

Detailed description

FAP-TK transgenic mice express an inducible suicide gene, Herpes simplex virus thymidine kinase (TK), in carcinoma-associated fibroblasts (CAF). The transgene promoter, Fap (fibroblast activation protein), encodes a serine protease that is expressed on activated fibroblasts and is found in a large percentage of human carcinomas. CAFs are involved in the growth, migration and progression of tumors. Following administration of ganciclovir (GCV), proliferating cells that express the FAP-TK transgene metabolize GCV to toxic nucleotide analogues and undergo cell death. Females hemizygous for the transgene are viable and fertile. Hemizygous males are viable and sterile. When FAP-TK mice are combined with a mouse model of pancreatic ductal adenocarcinoma (PDAC), suppression of FAP⁺ CAFs results in inhibition of tumor growth and increased survival. This strain may be useful for understanding the role of FAP+ myofibroblasts in tumor progression in the context of both orthotopic and autochthonous tumors.

FAP-TK transgenic mice are available on the BALB/c (this strain - Stock No. 035907) and C57BL/6J (Stock No. 034655) backgrounds.

Development

The FAP-TK transgenic construct contains a 5 kb sequence that includes the Fap (fibroblast activation protein) promoter and part of exon 1 inserted into the pORF-HSV1-TK vector, which contains the full coding sequence of the Herpes simplex virus thymidine kinase. The linearized construct was microinjected into the pronuclei of fertilized C57BL/6J. Founder line M was established. Mice carrying the transgene were backcrossed to BALB/cAnNCrl mice for a minimum of 10 generations. Upon arrival, female mice were bred to BALB/cByJ (Stock No. 001026) males for at least 1 generation to establish the colony.

Allele

Symbol: Tg(Fap-TK)MRkl
Name: transgene insertion M, Raghu Kalluri
MGI accession ID: MGI:6509143
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: FAP-TK
Marker symbol: Tg(Fap-TK)MRkl
Marker name: transgene insertion M, Raghu Kalluri
Chromosome: UN
Strain of origin: C57BL/6J
Site of expression: expressed on activated fibroblasts and is found in a large percentage of human carcinomas
Molecular note: The transgenic construct contains a 5 kb sequence including the Fap (fibroblast activation protein) promoter and part of exon 1 inserted into the pORF-HSV1-TK vector, which contains the full coding sequence of the Herpes simplex virus thymidine kinase.