These MMTV-TGFα mice express a transgene containing the normal allele of the human transforming growth factor alpha gene and adult females exhibit sebaceous gland hyperplasia and inadequate lactation in females.
Dr. Robert J. Coffey, Vanderbilt University Medical Center
The phenotype of TgN(MMTVTGFA)254Rjc transgenic mice is very similar to that of B6D2-TgN(MMTVTGFA)29Rjc (Stock No. 002373). Mice are viable and fertile, but lactate insufficiently to support the litter. Virgin transgenic mice show no mammary gland abnormalities prepubertally, but adult virgin mice have considerable alveolar gland hyperplasia. Pregnant transgenic mice show marked proliferation of the stromal cells, and alveolar secretion is markedly increased compared to nontransgenic mice. After multiple pregnancies, isolated adenocarcinomas develop. There is no apparent phenotypic effect in males. In females transgene expression was localized to the small ducts and alveoli in both virgin and pregnant mice as evidenced by in situ hybridization and by immunohistochemistry. Immunostaining also revealed some stromal staining in the hyperplastic areas. Egfr mRNA expression was also increased in mammary tissues expressing high levels of the transgene. Crosses between TGFA transgenic mice and TGFB1 transgenic mice demonstrate that these growth factors oppose each other's action on mammary gland development. The B6D2-TgN(MMTVTGFA)254Rjc line is notable for sebaceous gland hyperplasia, which occurs in both male and female mice. The hyperplasia was evidenced as multiple raised, white plaques and nodules on the abdominal skin. No dysplasia or sebaceous cell carcinoma was observed. High expression of TGFa mRNA and TGFa protein was detected in the areas of sebaceous hyperplasia.
To construct pMMTV-TGFa, a pKCR vector in which the SV40 early promoter region was replaced with complete MMTV LTR and a 925 bp human TGFa cDNA was inserted in the EcoRI site of b-globin exon 3. The 3.6 kb XhoI fragment was microinjected into (C57BL X DBA)F2 fertilized eggs. Transgenic mice are identified either by Southern blot using a b-globin exon 3 probe or by PCR. Transgenic lines were generated by mating founder animals to (C57BL X DBA/2)F1 males and females. No details of subsequent strain development were provided.
|Expressed Gene||TGFA, transforming growth factor alpha, human|
|Site of Expression|
|Allele Name||transgene insertion 254, Robert J Coffey|
|Allele Type||Transgenic (Inserted expressed sequence, Humanized sequence)|
|Gene Symbol and Name||Tg(MMTVTGFA)254Rjc, transgene insertion 254, Robert J Coffey|
|Promoter||MMTV, Mouse Mammary Tumor Virus, MMTV|
|Expressed Gene||TGFA, transforming growth factor alpha, human|
|Strain of Origin||(C57BL/6 x DBA/2)F2|
|Molecular Note||The transgene contains the mouse mammary tumor virus LTR and the normal allele of the human transforming growth factor alpha gene. The vector also contains exons 2 and 3 of the rabbit beta-globin gene. Lines 254, 257, 64 and 29 were produced.|
|Mutations Made By|| |
Dr. Robert Coffey, Vanderbilt University Medical Center
When maintaining a live colony, this strain is maintained by mating a (C57BL/6J x DBA/2)F1 female with transgenic carrier male. Female transgenic mice do not lactate.
When using the MMTV-TGFα mouse strain in a publication, please cite the originating article(s) and include JAX stock #002459 in your Materials and Methods section.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.