Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?pN1 Generation Definitions   Donating Investigator Dr. Tyler Jacks,   Massachusetts Institute of Technology

Description
Mice homozygous for this targeted mutation are viable and fertile and do not display any gross physical or behavioral abnormalities in this genetic background. No histologic abnormalities have been detected at birth or 2 months of age. The amount of mRNA in liver cells is reduced 5-fold. No protein of normal size is detected by Western blot analysis of mouse embryonic fibroblasts which also show normal growth characteristics in culture. A very small amount of a truncated form of the protein has been detected by immunoprecipitation and western blot analysis. This shorter form of p130 may come from alternative splicing. It is not known if this truncated form has any activity or not. This strain may be useful in studies of limb development or cancer.

Development
A targeting vector was designed to replace some sequences in exon 2 with a neomycin resistance cassette inserted in reverse orientation. The targeting vector was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Resultant chimeric male animals were crossed with C57BL/6 females. The strain was maintained on a mixed 129S2/SvPas and C57BL/6 background by the donating laboratory.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Rbl2

008177

B6;129S4-Rbl2tm2Tyj/J

View Strains carrying other alleles of Rbl2     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Rbl2^tm1Tyj/Rbl2⁺

        involves: 129S2/SvPas * C57BL/6

• normal phenotype
• no abnormal phenotype detected
  • heterozygotes appear normal and show no increase in morbidity or mortality up to 16 months of age relative to wild-type mice   (MGI Ref ID J:34725)

Rbl2^tm1Tyj/Rbl2^tm1Tyj

        involves: 129S2/SvPas * C57BL/6

• normal phenotype
• no abnormal phenotype detected
  • homozygotes are viable and fertile, and display no detectable histologic abnormalities at birth or at 2 months of age   (MGI Ref ID J:34725)
• cellular phenotype
• *normal* cellular phenotype
  • surprisingly, mouse embryonic fibroblasts derived from homozygous mutants exhibit normal growth characteristics in culture   (MGI Ref ID J:34725)
  • gel mobility shft analysis indicated that Rbl1 largely replaces Rbl2 as the major E2F-associated species in mutant fibroblasts   (MGI Ref ID J:34725)
• integument phenotype
• *normal* integument phenotype
  • newborn homozygotes display normal epidermal terminal differentiation relative to heterozygous mutant littermates   (MGI Ref ID J:82802)

View Research Applications

Research Applications

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

Cancer Research
Oncogenes

Developmental Biology Research
Limb Patterning Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Rbl2tm1Tyj
Allele Name		targeted mutation 1, Tyler Jacks
Allele Type		Targeted (knock-out)
Common Name(s)		p130-;
Mutation Made By		Dr. Tyler Jacks,   Massachusetts Institute of Technology
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Rbl2, retinoblastoma-like 2
Chromosome		8
Gene Common Name(s)		P130; Rb2;
Molecular Note		A neomycin resistance cassette replaced sequences in a proximal exon of the Rbl2 gene. Rbl2 mRNA levels in liver cells of homozygous mutant animals were reduced more than five fold compared to wild-type. Immunoblot analysis did not detect RBL2 protein in embryonic fibroblasts or in adult liver of homozygous mutant mice. [MGI Ref ID J:34725]

Genotyping

Genotyping Information

Genotyping Protocols

Rbl2^tm1Tyj, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Cobrinik D; Lee MH; Hannon G; Mulligan G; Bronson RT; Dyson N; Harlow E; Beach D; Weinberg RA; Jacks T. 1996. Shared role of the pRB-related p130 and p107 proteins in limb development. Genes Dev 10(13):1633-44. [PubMed: 8682294]  [MGI Ref ID J:34725]

Additional References

Rbl2^tm1Tyj related

Ajioka I; Martins RA; Bayazitov IT; Donovan S; Johnson DA; Frase S; Cicero SA; Boyd K; Zakharenko SS; Dyer MA. 2007. Differentiated horizontal interneurons clonally expand to form metastatic retinoblastoma in mice. Cell 131(2):378-90. [PubMed: 17956737]  [MGI Ref ID J:130181]

Angelis E; Garcia A; Chan SS; Schenke-Layland K; Ren S; Goodfellow SJ; Jordan MC; Roos KP; White RJ; MacLellan WR. 2008. A cyclin D2-Rb pathway regulates cardiac myocyte size and RNA polymerase III after biomechanical stress in adult myocardium. Circ Res 102(10):1222-9. [PubMed: 18420946]  [MGI Ref ID J:149022]

Garcia MA; Gallego P; Campagna M; Gonzalez-Santamaria J; Martinez G; Marcos-Villar L; Vidal A; Esteban M; Rivas C. 2009. Activation of NF-kB pathway by virus infection requires Rb expression. PLoS One 4(7):e6422. [PubMed: 19649275]  [MGI Ref ID J:151312]

Haigis K; Sage J; Glickman J; Shafer S; Jacks T. 2006. The related retinoblastoma (pRb) and p130 proteins cooperate to regulate homeostasis in the intestinal epithelium. J Biol Chem 281(1):638-47. [PubMed: 16258171]  [MGI Ref ID J:106339]

Harb G; Vasavada RC; Cobrinik D; Stewart AF. 2009. The retinoblastoma protein and its homolog p130 regulate the G1/S transition in pancreatic beta-cells. Diabetes 58(8):1852-62. [PubMed: 19509021]  [MGI Ref ID J:154413]

Harrington EA; Bruce JL; Harlow E; Dyson N. 1998. pRB plays an essential role in cell cycle arrest induced by DNA damage. Proc Natl Acad Sci U S A 95(20):11945-50. [PubMed: 9751770]  [MGI Ref ID J:119775]

Hurford RK Jr; Cobrinik D; Lee MH; Dyson N. 1997. pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes Dev 11(11):1447-63. [PubMed: 9192872]  [MGI Ref ID J:41047]

Liu Y; Clem B; Zuba-Surma EK; El-Naggar S; Telang S; Jenson AB; Wang Y; Shao H; Ratajczak MZ; Chesney J; Dean DC. 2009. Mouse fibroblasts lacking RB1 function form spheres and undergo reprogramming to a cancer stem cell phenotype. Cell Stem Cell 4(4):336-47. [PubMed: 19341623]  [MGI Ref ID J:149842]

MacLean HE; Guo J; Knight MC; Zhang P; Cobrinik D; Kronenberg HM. 2004. The cyclin-dependent kinase inhibitor p57(Kip2) mediates proliferative actions of PTHrP in chondrocytes. J Clin Invest 113(9):1334-43. [PubMed: 15124025]  [MGI Ref ID J:89721]

MacLellan WR; Garcia A; Oh H; Frenkel P; Jordan MC; Roos KP; Schneider MD. 2005. Overlapping roles of pocket proteins in the myocardium are unmasked by germ line deletion of p130 plus heart-specific deletion of Rb. Mol Cell Biol 25(6):2486-97. [PubMed: 15743840]  [MGI Ref ID J:97589]

MacPherson D; Sage J; Kim T; Ho D; McLaughlin ME; Jacks T. 2004. Cell type-specific effects of Rb deletion in the murine retina. Genes Dev 18(14):1681-94. [PubMed: 15231717]  [MGI Ref ID J:91406]

McEvoy J; Flores-Otero J; Zhang J; Nemeth K; Brennan R; Bradley C; Krafcik F; Rodriguez-Galindo C; Wilson M; Xiong S; Lozano G; Sage J; Fu L; Louhibi L; Trimarchi J; Pani A; Smeyne R; Johnson D; Dyer MA. 2011. Coexpression of normally incompatible developmental pathways in retinoblastoma genesis. Cancer Cell 20(2):260-75. [PubMed: 21840489]  [MGI Ref ID J:176061]

Mulligan GJ; Wong J; Jacks T. 1998. p130 is dispensable in peripheral T lymphocytes: evidence for functional compensation by p107 and pRB. Mol Cell Biol 18(1):206-20. [PubMed: 9418868]  [MGI Ref ID J:44897]

Reed CA; Mayhew CN; McClendon AK; Knudsen ES. 2010. Unique impact of RB loss on hepatic proliferation: tumorigenic stresses uncover distinct pathways of cell cycle control. J Biol Chem 285(2):1089-96. [PubMed: 19887370]  [MGI Ref ID J:159963]

Rocha-Sanchez SM; Scheetz LR; Contreras M; Weston MD; Korte M; McGee J; Walsh EJ. 2011. Mature Mice Lacking Rbl2/p130 Gene Have Supernumerary Inner Ear Hair Cells and Supporting Cells. J Neurosci 31(24):8883-93. [PubMed: 21677172]  [MGI Ref ID J:173537]

Rossi F; MacLean HE; Yuan W; Francis RO; Semenova E; Lin CS; Kronenberg HM; Cobrinik D. 2002. p107 and p130 Coordinately regulate proliferation, Cbfa1 expression, and hypertrophic differentiation during endochondral bone development. Dev Biol 247(2):271-85. [PubMed: 12086466]  [MGI Ref ID J:77813]

Ruiz S; Segrelles C; Bravo A; Santos M; Perez P; Leis H; Jorcano JL; Paramio JM. 2003. Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130. Development 130(11):2341-53. [PubMed: 12702649]  [MGI Ref ID J:82802]

Ruiz S; Segrelles C; Santos M; Lara MF; Paramio JM. 2004. Functional link between retinoblastoma family of proteins and the Wnt signaling pathway in mouse epidermis. Dev Dyn 230(3):410-8. [PubMed: 15188427]  [MGI Ref ID J:91212]

Sdek P; Zhao P; Wang Y; Huang CJ; Ko CY; Butler PC; Weiss JN; Maclellan WR. 2011. Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes. J Cell Biol 194(3):407-23. [PubMed: 21825075]  [MGI Ref ID J:176968]

Shin MK; Pitot HC; Lambert PF. 2012. Pocket proteins suppress head and neck cancer. Cancer Res 72(5):1280-9. [PubMed: 22237625]  [MGI Ref ID J:181495]

Simpson DS; Mason-Richie NA; Gettler CA; Wikenheiser-Brokamp KA. 2009. Retinoblastoma family proteins have distinct functions in pulmonary epithelial cells in vivo critical for suppressing cell growth and tumorigenesis. Cancer Res 69(22):8733-41. [PubMed: 19887614]  [MGI Ref ID J:154440]

Sindermann JR; Smith J; Kobbert C; Plenz G; Skaletz-Rorowski A; Solomon JL; Fan L; March KL. 2002. Direct evidence for the importance of p130 in injury response and arterial remodeling following carotid artery ligation. Cardiovasc Res 54(3):676-83. [PubMed: 12031714]  [MGI Ref ID J:102532]

Soeiro I; Mohamedali A; Romanska HM; Lea NC; Child ES; Glassford J; Orr SJ; Roberts C; Naresh KN; Lalani el-N; Mann DJ; Watson RJ; Thomas NS; Lam EW. 2006. p27Kip1 and p130 cooperate to regulate hematopoietic cell proliferation in vivo. Mol Cell Biol 26(16):6170-84. [PubMed: 16880527]  [MGI Ref ID J:111578]

Vidal A; Zacharoulis S; Guo W; Shaffer D; Giancotti F; Bramley AH; de la Hoz C; Jensen KK; Kato D; MacDonald DD; Knowles J; Yeh N; Frohman LA; Rafii S; Lyden D; Koff A. 2005. p130Rb2 and p27kip1 cooperate to control mobilization of angiogenic progenitors from the bone marrow. Proc Natl Acad Sci U S A 102(19):6890-5. [PubMed: 15867156]  [MGI Ref ID J:99064]

Wikenheiser-Brokamp KA. 2006. Retinoblastoma family proteins: insights gained through genetic manipulation of mice. Cell Mol Life Sci 63(7-8):767-80. [PubMed: 16465443]  [MGI Ref ID J:108542]

Yeh N; Miller JP; Gaur T; Capellini TD; Nikolich-Zugich J; de la Hoz C; Selleri L; Bromage TG; van Wijnen AJ; Stein GS; Lian JB; Vidal A; Koff A. 2007. Cooperation between p27 and p107 during endochondral ossification suggests a genetic pathway controlled by p27 and p130. Mol Cell Biol 27(14):5161-71. [PubMed: 17502351]  [MGI Ref ID J:123662]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, homozygotes may be bred.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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.

See Terms of Use tab for General Terms and Conditions

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 Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

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

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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

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 and PRODUCTS 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.