Overview

Also Known As: Atg6-

These autophagy-related beclin 1 (Becn1) knockout mice exhibit late onset lung carcinomas, hepatocellular carcinomas and lymphomas and may be useful for studying autophagy, negative cell growth and tumor suppression.

Donating Investigator

Beth Levine, University of Texas Southwestern Medical

Genetic overview

Genetic Background	Generation

Becn1^tm1Blev

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Becn1	beclin 1, autophagy related

View Genetics

Research Applications

Cancer Research
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Monoallelic deletion of the autophagy related beclin 1 (Becn1) gene is associated with 40-75% of human breast, ovarian and prostate cancers. 30% of mice heterozygous for the Becn1 allele exhibit tumors by 13-18 months of age. Tumor types include: lung carcinomas, hepatocellular carcinomas and lymphomas. In addition, mice develop hepatitis B virus-induced neoplasia, increased cellular proliferation and reduced autophagy. Homozygous deletion of the targeted allele results in embryonic lethality. Of note, mice on a C57BL/6 background have a brownish (agouti) coat color which is believed to be a result of the effect of the Becn1 mutation on melanogenesis. These mice may be useful for studies involving autophagy and negative cell growth and tumor suppression.

Development

A targeting vector was designed to replace exons 1 and 2 with a neomycin resistance (neo) cassette. The construct was electroporated into 129X1/SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to C57BL/6. Offspring were backcrossed to C57BL/6 for 50 generations, however, mice retain a brownish (agouti) coat color, which is believed to be a result of the role of Becn1 in melanogenesis. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Qu X; Yu J; Bhagat G; Furuya N; Hibshoosh H; Troxel A; Rosen J; Eskelinen EL; Mizushima N; Ohsumi Y; Cattoretti G; Levine B. 2003. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 112(12):1809-20PubMed: 14638851 MGI: J:86953

View All References

Genetics

Becn1^tm1Blev

Allele Symbol: Becn1^tm1Blev

Allele Name	targeted mutation 1, Beth Levine
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Becn1^tm1Blev; targeted mutation 1, Beth Levine
Gene Symbol and Name	Becn1, beclin 1, autophagy related
Gene Synonym(s)	ATG6; MGC:6843; VPS30; beclin1; Atg6; Beclin1
Strain of Origin	129X1/SvJ
Chromosome	11
Molecular Note	Exons 1 and 2 were replace with a neomycin selection cassette inserted by homologous recombination.
Mutations Made By	Beth Levine, University of Texas Southwestern Medical

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Cancer Research
- Increased Tumor Incidence
  - Hepatomas: hepatacellular carcinoma
  - Adenomas: lung
  - Lymphomas
Developmental Biology Research
- Embryonic Lethality (Homozygous)

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Becn1^tm1Blev/Becn1⁺
involves: 129X1/SvJ * C57BL/6J

cellular phenotype

impaired autophagy
- germinal center B lymphocytes have fewer autophagic vacuoles than wild-type lymphocytes 10 days after immunization with sheep red blood cells, indicating reduced autophagic activity

integument phenotype

abnormal mammary gland duct morphology
- hyperproliferation of mammary ductal epithelial cells in the terminal end buds
- mammary ducts are frequently abnormal, with multiple layers of epithelial cells and intraluminal collections of epithelial cells
- mammary ducts show increase in DNA synthesis

increased mammary gland tumor incidence
- proliferative lesions (mammary intraepithelial neoplasia, adenomyoepithelioma, and acinar neoplasia) are present in mammary gland of 13 to 18 month old mutants

liver/biliary system phenotype

increased hepatocellular carcinoma incidence
- well-differentiated hepatocellular carcinomas

mortality/aging

premature death
- mutants show some tumor-associated mortality at 6 to 8 months of age

neoplasm

increased follicular lymphoma incidence

increased hepatocellular carcinoma incidence
- well-differentiated hepatocellular carcinomas

increased histiocytic sarcoma incidence

increased lung adenocarcinoma incidence
- lung cancers show features of well-differentiated human papillary adenocarcinomas

increased lung adenoma incidence
- logic atypia
- mutants have an increased frequency of lung lesions in earlier stages of neoplasia, including hyperplastic alveolar epithelium resembling human atypical adenomatous hyperplasia and bronchioalveolar adenomas composed of monomorphous cells with minimal cytologic atypia

increased lung carcinoma incidence
- greater number of and larger lung carcinomas than in wild-type mice

increased lymphoma incidence
- develop lymphomas that occur more frequently, at an earlier age, are more likely to present as palpable masses than in wild-type, including diffuse large-cell lymphoma, follicular lymphoma, immunoblastic variant of diffuse large-cell lymphoma, anaplastic plasmacytoma, and histiocytic sarcoma
- plasmacytoma, and histiocytic sarcoma

increased malignant tumor incidence
- mutants have a higher probability of having a malignancy (30%) than wild-type (14%); malignancies do not contain mutations in the wild-type Becn1 allele

increased mammary gland tumor incidence
- proliferative lesions (mammary intraepithelial neoplasia, adenomyoepithelioma, and acinar neoplasia) are present in mammary gland of 13 to 18 month old mutants

increased plasmacytoma incidence
- anaplastic plasmacytoma

increased tumor incidence
- 15% of mutants at 13-18 months of age exhibit palpable tumors compared to 1% of wild-type mice

endocrine/exocrine gland phenotype

abnormal mammary gland duct morphology
- hyperproliferation of mammary ductal epithelial cells in the terminal end buds
- mammary ducts are frequently abnormal, with multiple layers of epithelial cells and intraluminal collections of epithelial cells
- mammary ducts show increase in DNA synthesis

increased mammary gland tumor incidence
- proliferative lesions (mammary intraepithelial neoplasia, adenomyoepithelioma, and acinar neoplasia) are present in mammary gland of 13 to 18 month old mutants

respiratory system phenotype

increased lung adenocarcinoma incidence
- lung cancers show features of well-differentiated human papillary adenocarcinomas

increased lung adenoma incidence
- logic atypia
- mutants have an increased frequency of lung lesions in earlier stages of neoplasia, including hyperplastic alveolar epithelium resembling human atypical adenomatous hyperplasia and bronchioalveolar adenomas composed of monomorphous cells with minimal cytologic atypia

increased lung carcinoma incidence
- greater number of and larger lung carcinomas than in wild-type mice

hematopoietic system phenotype

increased spleen germinal center number
- mutants show an increase in the number of germinal centeres in the spleens following immunization with sheep red blood cells at 2 months of age

increased spleen germinal center size
- mutants show an increase in the size of germinal centers in the spleens following immunization with sheep red blood cells at 2 months of age

homeostasis/metabolism phenotype

impaired autophagy
- germinal center B lymphocytes have fewer autophagic vacuoles than wild-type lymphocytes 10 days after immunization with sheep red blood cells, indicating reduced autophagic activity

immune system phenotype

abnormal immune system morphology
- increase in frequency of extranodal, splenic, and nodal lymphoproliferative disease

increased spleen germinal center number
- mutants show an increase in the number of germinal centeres in the spleens following immunization with sheep red blood cells at 2 months of age

increased spleen germinal center size
- mutants show an increase in the size of germinal centers in the spleens following immunization with sheep red blood cells at 2 months of age

Genotype: Becn1^tm1Blev/Becn1^tm1Blev
involves: 129X1/SvJ * C57BL/6J

mortality/aging

prenatal lethality, complete penetrance
- embryonic lethality, time not specified

Genotype: Becn1^tm1Blev/Becn1^tm1Blev
involves: 129X1/SvJ

cardiovascular system phenotype

decreased myocardial infarction size
- following ischemia and reperfusion with SB216763 (a GSK3b inhibitor) and rapamycin treatment

increased myocardial infarction size
- following 2 hours of ischemia without reperfusion
- not affected by treatment with SB216763 (a GSK3b inhibitor) and rapamycin

homeostasis/metabolism phenotype

decreased myocardial infarction size
- following ischemia and reperfusion with SB216763 (a GSK3b inhibitor) and rapamycin treatment

increased myocardial infarction size
- following 2 hours of ischemia without reperfusion
- not affected by treatment with SB216763 (a GSK3b inhibitor) and rapamycin

References

Qu X; Yu J; Bhagat G; Furuya N; Hibshoosh H; Troxel A; Rosen J; Eskelinen EL; Mizushima N; Ohsumi Y; Cattoretti G; Levine B. 2003. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 112(12):1809-20PubMed: 14638851 MGI: J:86953

Additional - Becn1^tm1Blev related

Technical Support

Contact Technical Support

Genotyping Protocols
- Separated PCR: Becn1^tm1Blev
- Separated MCA: Becn1^tm1Blev
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are not viable. Of note, mice on a C57BL/6 background have a brown coat color which is believed to be a result of the Becn1 mutation on melanogenesis.
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the Atg6- mouse strain in a publication, please cite the originating article(s) and include JAX stock #018429 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Becn1<tm1Blev>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"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.

No Warranty

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.

Credit for PRODUCTS or SERVICES

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.

Animal Care and Use for SERVICES

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.

No Liability

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.

Also Known As: Atg6-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Becn1tm1Blev

Allele Symbol: Becn1tm1Blev

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Becn1tm1Blev/Becn1+involves: 129X1/SvJ * C57BL/6J

cellular phenotype

integument phenotype

liver/biliary system phenotype

mortality/aging

neoplasm

endocrine/exocrine gland phenotype

respiratory system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Becn1tm1Blev/Becn1tm1Blevinvolves: 129X1/SvJ * C57BL/6J

mortality/aging

Genotype: Becn1tm1Blev/Becn1tm1Blevinvolves: 129X1/SvJ

cardiovascular system phenotype

homeostasis/metabolism phenotype

References

Additional - Becn1tm1Blev related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Becn1^tm1Blev

Allele Symbol: Becn1^tm1Blev

Genotype: Becn1^tm1Blev/Becn1⁺
involves: 129X1/SvJ * C57BL/6J

Genotype: Becn1^tm1Blev/Becn1^tm1Blev
involves: 129X1/SvJ * C57BL/6J

Genotype: Becn1^tm1Blev/Becn1^tm1Blev
involves: 129X1/SvJ

Additional - Becn1^tm1Blev related