Strain Name:

FVB/N-Tg(MMTV-Notch4)3Rnc/J

Stock Number:

002437

Availability:

Repository-Cryopreserved

Use Restrictions Apply, see Terms of Use

Description

Strain Information

Former Names FVB/N-TgN(MMTVInt3)3Rnc    (Changed: 15-DEC-04 )
TgN(MMTVNotch4)3Rnc    (Changed: 15-DEC-04 )
Type Mutant Strain; Transgenic;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
 
Donating Investigator Robert Callahan,   National Institutes of Health

Description
Male mice transgenic for the Notch4 gene (previously called Int3) are sterile, and females fail to lactate. Mammary tissue of females does not develop completely, exhibiting dramatic inhibition of alveolar-lobular development and reduced penetration of the mammary fat pad by ductal epithelium. Glandular epithelia of tissues expressing the activated form of Notch4 generally display severe ductal hyperplasia. Salivary glands fail to differentiate completely. Male transgenic mice exhibit severe epididymal hyperplasia, which is thought to be the cause of their sterility. Both male and female mice develop focal adenomas of the mammary and salivary glands.

Development
Transgenic mice were generated using a 7.5 kb genomic DNA fragment containing the 3' portion of the mouse Notch4 gene under the influence of the Czech II MMTV LTR. FVB/N embryos were microinjected. The FF1 line was established by superovulating and mating the female founder to a nontransgenic FVB male, isolating single-cell embryos, and transferring them to a pseudopregnant CD1 mouse. Thereafter, mice newly born to subsequent FF1 Notch4 transgenic mice were routinely moved to foster mothers.

Control Information

  Control
   Noncarrier
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of MMTV     (18 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(MMTV-Notch4)3Rnc/0

        involves: FVB/N
  • endocrine/exocrine gland phenotype
  • abnormal gland morphology (MGI Ref ID J:11644)
    • glands of the nasal mucosa and maxiallary sinus contain proliferating immature ductal cells and are incompletely differentiated
    • abnormal Harderian gland morphology (MGI Ref ID J:11644)
      • hyperplasia of immature ductal cells is seen frequently in the Harderian gland
    • abnormal lacrimal gland morphology (MGI Ref ID J:11644)
      • hyperplasia of immature ductal cells is seen frequently in the extraorbital lacrimal gland
    • abnormal mammary gland morphology (MGI Ref ID J:11644)
      • hyperplastic nodular lesions and multifocal neoplastic lesions at multiple sites in the fat pad of mammary glands
      • mammary gland secretory lobules and alveoli are absent in parous females
      • abnormal mammary gland development (MGI Ref ID J:11644)
        • inguinal mammary gland development is incomplete, with mutants showing a truncated version of the normal glandular penetration of the mammary fat pat and absence of end buds
        • mammary gland alveolar and ductal structures are sparse
        • in parous females, lobular-alveolar development is incomplete; secretory lobules and alveoli are largely missing
      • mammary ductal hyperplasia (MGI Ref ID J:11644)
    • abnormal salivary gland morphology (MGI Ref ID J:11644)
      • major and minor salivary glands show severe ductular hyperplasia and incomplete differentiation
      • proliferating ductules appear to consist of immature cell types
      • abnormal parotid gland morphology (MGI Ref ID J:11644)
        • hyperplastic lesions of the parotid salivary glands
      • abnormal sublingual gland morphology (MGI Ref ID J:11644)
        • hyperplastic lesions of the sublingual salivary glands
        • occasionally observe serous metaplasia in the sublingual gland
      • abnormal submandibular gland morphology (MGI Ref ID J:11644)
        • hyperplastic lesions of the submandibular salivary glands
  • abnormal lactation (MGI Ref ID J:11644)
    • parous females fail to lactate
  • tumorigenesis
  • increased metastatic potential (MGI Ref ID J:11644)
    • lung metastases in 4 of 7 mutants with mammary tumors
  • mammary adenocarcinoma (MGI Ref ID J:11644)
    • focal and often multiple poorly differentiated mammary adenocarcinomas appear in the majority of transgenics between 2 and 7 months of age
  • salivary adenocarcinoma (MGI Ref ID J:11644)
    • focal and often multiple poorly differentiated salivary adenocarcinomas appear in the majority of transgenics between 2 and 6 months of age
  • reproductive system phenotype
  • abnormal epididymis epithelium morphology (MGI Ref ID J:11644)
    • the pseudostratified epithelium of the epididymis is disorganized
  • abnormal lactation (MGI Ref ID J:11644)
    • parous females fail to lactate
  • abnormal mammary gland morphology (MGI Ref ID J:11644)
    • hyperplastic nodular lesions and multifocal neoplastic lesions at multiple sites in the fat pad of mammary glands
    • mammary gland secretory lobules and alveoli are absent in parous females
    • abnormal mammary gland development (MGI Ref ID J:11644)
      • inguinal mammary gland development is incomplete, with mutants showing a truncated version of the normal glandular penetration of the mammary fat pat and absence of end buds
      • mammary gland alveolar and ductal structures are sparse
      • in parous females, lobular-alveolar development is incomplete; secretory lobules and alveoli are largely missing
    • mammary ductal hyperplasia (MGI Ref ID J:11644)
  • enlarged epididymis (MGI Ref ID J:11644)
    • males exhibit severe epididymal hyperplasia
  • male infertility (MGI Ref ID J:11644)
  • oligozoospermia (MGI Ref ID J:11644)
    • epididymis occasionally contains reduced sperm count
  • digestive/alimentary phenotype
  • abnormal salivary gland morphology (MGI Ref ID J:11644)
    • major and minor salivary glands show severe ductular hyperplasia and incomplete differentiation
    • proliferating ductules appear to consist of immature cell types
    • abnormal parotid gland morphology (MGI Ref ID J:11644)
      • hyperplastic lesions of the parotid salivary glands
    • abnormal sublingual gland morphology (MGI Ref ID J:11644)
      • hyperplastic lesions of the sublingual salivary glands
      • occasionally observe serous metaplasia in the sublingual gland
    • abnormal submandibular gland morphology (MGI Ref ID J:11644)
      • hyperplastic lesions of the submandibular salivary glands
  • vision/eye phenotype
  • abnormal Harderian gland morphology (MGI Ref ID J:11644)
    • hyperplasia of immature ductal cells is seen frequently in the Harderian gland
  • abnormal lacrimal gland morphology (MGI Ref ID J:11644)
    • hyperplasia of immature ductal cells is seen frequently in the extraorbital lacrimal gland
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Cancer Research
Increased Tumor Incidence (Adenomas)
Increased Tumor Incidence (Mammary Gland Tumors)
Increased Tumor Incidence (Other Tissues/Organs)

Endocrine Deficiency Research
Gonad Defects
Mammary Gland Defects

Reproductive Biology Research
Endocrine Deficiencies Affecting Gonads
Fertility Defects

Research Tools
Cancer Research
Endocrine Deficiency Research
Reproductive Biology Research

Notch4 related

Cancer Research
Increased Tumor Incidence (Mammary Gland Tumors)

Genes & Alleles

Gene & Allele Information

Allele Symbol Tg(MMTV-Notch4)3Rnc
Allele Name transgene insertion 3, Robert Callahan
Allele Type Transgenic (random, expressed)
Common Name(s) FF1 int-3; FVB-3; MMTV LTR-INT3; MMTV-int-3; TgN(MMTVInt3)3Rnc;
Strain of OriginFVB/N
Expressed Gene Notch4, Notch gene homolog 4 (Drosophila), mouse, laboratory
Promoter MMTV, Mouse Mammary Tumor Virus, MMTV
General Note Six founder mice with similar phenotypes noted. One line established.
Molecular Note A 7.5 kb genomic fragment derived from a Czech II mammary tumor was used to generate transgenic mice. The fragment contained MMTV envelope and 3' LTR sequences and a truncated portion of the mouse Notch4 gene. [MGI Ref ID J:11644]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(MMTV-Notch4)3Rnc, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Jhappan C; Gallahan D; Stahle C; Chu E; Smith GH; Merlino G; Callahan R. 1992. Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev 6(3):345-55. [PubMed: 1372276]  [MGI Ref ID J:11644]

Additional References

Tg(MMTV-Notch4)3Rnc related

Smith GH; Gallahan D; Diella F; Jhappan C; Merlino G; Callahan R. 1995. Constitutive expression of a truncated INT3 gene in mouse mammary epithelium impairs differentiation and functional development. Cell Growth Differ 6(5):563-77. [PubMed: 7544153]  [MGI Ref ID J:26600]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryHemizygous males are sterile, females can develop tumors as soon as six weeks. Hemizygous females do not lactate. Mating scheme:Tg/+ females to a +/+ males and foster every litter to a mother that lactates. Expected coat color from breeding:Albino

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
*Price(s) in US dollars ($)

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
*Price(s) in US dollars ($)

Additional Supply Details

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.

Control Information

  Control
   Noncarrier
   001800 FVB/NJ
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
  International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions


See Terms of Use


The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
Ordering and Purchasing Information

      Purchasing Information
      JAX® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


OncoMouse® requires a license from DuPont, see Licenses for Strains with OncoMouse® Technology.

Contact information

General inquiries

Contracts Administration

phone:207-288-6470
fax:207-288-6655

JAX® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. THE LABORATORY 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 MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.


(3.2)