FVB/N-Tg(KRT14-HPV16E7)2304Plam/J

Stock number: 037879
Product name: K14E7
Research areas: Cancer Research, Dermatology Research, Developmental Biology Research, Research Tools, Sensorineural Research, Virology Research

Description

K14E7 transgenic mice carry a human keratin 14 (KRT14) promoter directing expression of the E7 gene from high-risk human papillomavirus type 16 (HPV16) to the basal layer of epithelia. Mice develop epidermal and hyperkeratosis. Skin tumors are found in 3 out of 30 mice by 10.6 months of age. This strain may be useful for research involving HPVs and tumorigenesis.

Of note, the K14E6 transgenic strain (expressing HPV16 E6) is distributed as FVB/N-Tg(KRT14-HPV16E6)5737Plam/J (Stock No. 037878).

Detailed description

Human papillomavirus type 16 (HPV16) is a high-risk small DNA tumor virus that causes papillomas in skin, genitalia, and the upper respiratory tract. HPV16 is associated with cervical cancer.  Cancer cells found in HPV-infected individuals often have the HPV genome integrated into the cellular genome. The integration includes the early region of the HPV genome containing the E6 and E7 genes. In cell cultures E6 can immortalize primary human mammary epithelial cells and E7 can transform primary human keratinocytes. E6 has been found to associate with TRP53 and lead to TRP53 degradation through the ubiquitin proteasome pathway. E7 has been found to associate with RB (retinoblastoma) and interfere with RB binding and inactivation of the E2F transcription factor.

K14E7 transgenic (low copy founder 2304) mice carry a human keratin 14 (KRT14) promoter directing expression of E7 gene from human papillomavirus type 16 (HPV16). The KRT14 promoter directs expression to the basal layer of the epithelia. Mice homozygous for the transgene are viable and fertile, however homozygous females have trouble nursing. Stunted growth is seen in some homozygous mice.  Hemizygous K14E7 mice develop epidermal hyperplasia (skin, mouth palate, esophagus, forestomach, exocervix), and hyperkeratosis. Mice also exhibit wrinkled skin (neonates), cataracts and scruffy fur. Skin tumors in the torso and limbs develop in 3 out of 30 mice at around 10.6 months of age.  Most tumors found in K14E7 mice are benign.

Of note, the K14E6 transgenic strain (expressing HPV16 E6) is distributed as FVB/N-Tg(KRT14-HPV16E6)5737Plam/J (Stock No. 037878).

Development

The K14E7 transgenic construct contains a human keratin 14 (KRT14) promoter directing expression of human papillomavirus type 16 (HPV16) fragment (nucleotides 79-883) containing the open reading frames of the E6 and E7 genes followed by a polyA signal. The insertion of a translational termination linker (TTL) in E6 disrupts E6 translation. The linearized construct was microinjected into the pronuclei of fertilized FVB/NJ mice. Founder line 2304 expresses 2 copies of the transgene; the insertion site is unknown. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ oocytes (Stock No. 001800).

Allele

Symbol: Tg(KRT14-HPV16E7)2304Plam
Name: transgene insertion 2304, Paul F Lambert
MGI accession ID: MGI:3514313
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: 2304; K14E7; K14-E7; K14E7^WT; K14HPV16E7
Marker symbol: Tg(KRT14-HPV16E7)2304Plam
Marker name: transgene insertion 2304, Paul F Lambert
Marker synonyms: 2304; K14E7; K14-E7; K14HPV16E7
Chromosome: UN
Strain of origin: FVB/NTac
Molecular note: This transgene contains a HPV16 fragment (nt79-883) encompassing both the E6 and E7 genes along with promoter, 3'UTR and polyA sequences from human KRT14. Only E7 is expressed due to the presence of a translation termination linker in the N terminal region of the E6 gene. Transgene expression is targeted toward epithelial tissues. Mice derived from founder 2304 had 2 copies of the transgene. Mice derived from founder 2332 had 7-8 copies of the transgene. this is a representative record for lines 2304 and 2332 which have identical phenotypes.