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 Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Dr. Tyler Jacks,   Massachusetts Institute of Technology

Description
These mice possess loxP sites on either side of exon 3 of the targeted gene. Mice that are homozygous for this conditional mutant allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. This strain may be useful in cancer or cell cycle/senescence studies.

Development
A targeting vector was designed to introduce a puromycin resistance cassette flanked by loxP sites to intron 3, and an additional loxP site to intron 2. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Transient Cre excision was used to excise the puromycin cassette, leaving exon 3 flanked by loxP sites. This strain was maintained on a mixed background composed of C57BL/6 and 129 by the donating laboratory.

Related Strains

Strains carrying other alleles of Rb1

002082	129S-Rb1tm1Tyj/J
002102	B6.129S2-Rb1tm1Tyj/J
002546	C3Ou.129S2-Rb1tm1Tyj/J
002900	FVB.129S2(B6)-Rb1tm1Tyj/J

View Strains carrying other alleles of Rb1     (4 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Bladder Cancer   (RB1) Osteogenic Sarcoma   (RB1) Retinoblastoma; RB1   (RB1) Small Cell Cancer of the Lung   (RB1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Rb1^tm3Tyj/Rb1^tm3Tyj

        Background Not Specified   (conditional)

• cellular phenotype
• polyploidy
  • adult liver cells of mice injected intrasplenically with an adenovirus expressing Cre recombinase exhibit an increase in polyploidy   (MGI Ref ID J:172430)
• tumorigenesis
• *normal* tumorigenesis
  • mice injected intrasplenically with an adenovirus expressing Cre recombinase do not develop liver tumors   (MGI Ref ID J:172430)

View Research Applications

Research Applications

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

Cancer Research
Tumor Suppressor Genes

Cell Biology Research
Cell Cycle Regulation

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Rb1tm3Tyj
Allele Name		targeted mutation 3, Tyler Jacks
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Rb12lox; Rbf; RbloxP;
Mutation Made By		Dr. Tyler Jacks,   Massachusetts Institute of Technology
Gene Symbol and Name		Rb1, retinoblastoma 1
Chromosome		14
Gene Common Name(s)		OSRC; RB; Rb-1; p105-Rb; pRb; pp110;
Molecular Note		Single loxP sites flank exon 3. [MGI Ref ID J:81643]

Genotyping

Genotyping Information

Genotyping Protocols

Rb1^tm3Tyj, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sage J; Miller AL; Perez-Mancera PA; Wysocki JM; Jacks T. 2003. Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry. Nature 424(6945):223-8. [PubMed: 12853964]  [MGI Ref ID J:84407]

Additional References

Rb1^tm3Tyj related

Balsitis S; Dick F; Dyson N; Lambert PF. 2006. Critical Roles for Non-pRb Targets of Human Papillomavirus Type 16 E7 in Cervical Carcinogenesis. Cancer Res 66(19):9393-400. [PubMed: 17018593]  [MGI Ref ID J:113382]

Balsitis S; Dick F; Lee D; Farrell L; Hyde RK; Griep AE; Dyson N; Lambert PF. 2005. Examination of the pRb-dependent and pRb-independent functions of E7 in vivo. J Virol 79(17):11392-402. [PubMed: 16103190]  [MGI Ref ID J:101623]

Balsitis SJ; Sage J; Duensing S; Munger K; Jacks T; Lambert PF. 2003. Recapitulation of the effects of the human papillomavirus type 16 E7 oncogene on mouse epithelium by somatic Rb deletion and detection of pRb-independent effects of E7 in vivo. Mol Cell Biol 23(24):9094-103. [PubMed: 14645521]  [MGI Ref ID J:86866]

Berman SD; Calo E; Landman AS; Danielian PS; Miller ES; West JC; Fonhoue BD; Caron A; Bronson R; Bouxsein ML; Mukherjee S; Lees JA. 2008. Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. Proc Natl Acad Sci U S A 105(33):11851-6. [PubMed: 18697945]  [MGI Ref ID J:139697]

Calo E; Quintero-Estades JA; Danielian PS; Nedelcu S; Berman SD; Lees JA. 2010. Rb regulates fate choice and lineage commitment in vivo. Nature 466(7310):1110-4. [PubMed: 20686481]  [MGI Ref ID J:163313]

Chen H; Gu X; Liu Y; Wang J; Wirt SE; Bottino R; Schorle H; Sage J; Kim SK. 2011. PDGF signalling controls age-dependent proliferation in pancreatic beta-cells. Nature 478(7369):349-55. [PubMed: 21993628]  [MGI Ref ID J:177411]

Conkrite K; Sundby M; Mukai S; Thomson JM; Mu D; Hammond SM; Macpherson D. 2011. miR-17~92 cooperates with RB pathway mutations to promote retinoblastoma. Genes Dev 25(16):1734-45. [PubMed: 21816922]  [MGI Ref ID J:174680]

Dooley AL; Winslow MM; Chiang DY; Banerji S; Stransky N; Dayton TL; Snyder EL; Senna S; Whittaker CA; Bronson RT; Crowley D; Barretina J; Garraway L; Meyerson M; Jacks T. 2011. Nuclear factor I/B is an oncogene in small cell lung cancer. Genes Dev 25(14):1470-5. [PubMed: 21764851]  [MGI Ref ID J:174756]

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]

Ho VM; Schaffer BE; Karnezis AN; Park KS; Sage J. 2009. The retinoblastoma gene Rb and its family member p130 suppress lung adenocarcinoma induced by oncogenic K-Ras. Oncogene 28(10):1393-9. [PubMed: 19151761]  [MGI Ref ID J:147590]

Ianari A; Natale T; Calo E; Ferretti E; Alesse E; Screpanti I; Haigis K; Gulino A; Lees JA. 2009. Proapoptotic function of the retinoblastoma tumor suppressor protein. Cancer Cell 15(3):184-94. [PubMed: 19249677]  [MGI Ref ID J:145939]

Lee EY; Yuan TL; Danielian PS; West JC; Lees JA. 2009. E2F4 cooperates with pRB in the development of extra-embryonic tissues. Dev Biol 332(1):104-15. [PubMed: 19433082]  [MGI Ref ID J:152869]

Lu Z; Marcelin G; Bauzon F; Wang H; Fu H; Dun SL; Zhao H; Li X; Jo YH; Wardlaw S; Dun N; Chua S Jr; Zhu L. 2013. pRb is an obesity suppressor in hypothalamus and high-fat diet inhibits pRb in this location. EMBO J 32(6):844-57. [PubMed: 23403926]  [MGI Ref ID J:195318]

MacPherson D; Conkrite K; Tam M; Mukai S; Mu D; Jacks T. 2007. Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification. EMBO J 26(3):784-94. [PubMed: 17235288]  [MGI Ref ID J:119919]

MacPherson D; Sage J; Crowley D; Trumpp A; Bronson RT; Jacks T. 2003. Conditional mutation of Rb causes cell cycle defects without apoptosis in the central nervous system. Mol Cell Biol 23(3):1044-53. [PubMed: 12529408]  [MGI Ref ID J:81643]

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]

Pajcini KV; Corbel SY; Sage J; Pomerantz JH; Blau HM. 2010. Transient inactivation of Rb and ARF yields regenerative cells from postmitotic mammalian muscle. Cell Stem Cell 7(2):198-213. [PubMed: 20682446]  [MGI Ref ID J:163316]

Park KS; Martelotto LG; Peifer M; Sos ML; Karnezis AN; Mahjoub MR; Bernard K; Conklin JF; Szczepny A; Yuan J; Guo R; Ospina B; Falzon J; Bennett S; Brown TJ; Markovic A; Devereux WL; Ocasio CA; Chen JK; Stearns T; Thomas RK; Dorsch M; Buonamici S; Watkins DN; Peacock CD; Sage J. 2011. A crucial requirement for Hedgehog signaling in small cell lung cancer. Nat Med 17(11):1504-8. [PubMed: 21983857]  [MGI Ref ID J:178123]

Saddic LA; Wirt S; Vogel H; Felsher DW; Sage J. 2011. Functional Interactions between Retinoblastoma and c-MYC in a Mouse Model of Hepatocellular Carcinoma. PLoS One 6(5):e19758. [PubMed: 21573126]  [MGI Ref ID J:172430]

Schaffer BE; Park KS; Yiu G; Conklin JF; Lin C; Burkhart DL; Karnezis AN; Sweet-Cordero EA; Sage J. 2010. Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma. Cancer Res 70(10):3877-83. [PubMed: 20406986]  [MGI Ref ID J:160148]

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]

Shin MK; Sage J; Lambert PF. 2012. Inactivating all three rb family pocket proteins is insufficient to initiate cervical cancer. Cancer Res 72(20):5418-27. [PubMed: 22942253]  [MGI Ref ID J:192917]

Srinivasan SV; Mayhew CN; Schwemberger S; Zagorski W; Knudsen ES. 2007. RB loss promotes aberrant ploidy by deregulating levels and activity of DNA replication factors. J Biol Chem 282(33):23867-77. [PubMed: 17556357]  [MGI Ref ID J:124806]

Strati K; Lambert PF. 2007. Role of Rb-dependent and Rb-independent functions of papillomavirus E7 oncogene in head and neck cancer. Cancer Res 67(24):11585-93. [PubMed: 18089787]  [MGI Ref ID J:130800]

Viatour P; Ehmer U; Saddic LA; Dorrell C; Andersen JB; Lin C; Zmoos AF; Mazur PK; Schaffer BE; Ostermeier A; Vogel H; Sylvester KG; Thorgeirsson SS; Grompe M; Sage J. 2011. Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway. J Exp Med 208(10):1963-76. [PubMed: 21875955]  [MGI Ref ID J:177573]

Viatour P; Somervaille TC; Venkatasubrahmanyam S; Kogan S; McLaughlin ME; Weissman IL; Butte AJ; Passegue E; Sage J. 2008. Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family. Cell Stem Cell 3(4):416-28. [PubMed: 18940733]  [MGI Ref ID J:149791]

Walkley CR; Orkin SH. 2006. Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells. Proc Natl Acad Sci U S A 103(24):9057-62. [PubMed: 16754850]  [MGI Ref ID J:111063]

Walkley CR; Qudsi R; Sankaran VG; Perry JA; Gostissa M; Roth SI; Rodda SJ; Snay E; Dunning P; Fahey FH; Alt FW; McMahon AP; Orkin SH. 2008. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev 22(12):1662-76. [PubMed: 18559481]  [MGI Ref ID J:136693]

Wang H; Bauzon F; Ji P; Xu X; Sun D; Locker J; Sellers RS; Nakayama K; Nakayama KI; Cobrinik D; Zhu L. 2010. Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/- mice. Nat Genet 42(1):83-8. [PubMed: 19966802]  [MGI Ref ID J:155967]

Wirt SE; Adler AS; Gebala V; Weimann JM; Schaffer BE; Saddic LA; Viatour P; Vogel H; Chang HY; Meissner A; Sage J. 2010. G1 arrest and differentiation can occur independently of Rb family function. J Cell Biol 191(4):809-25. [PubMed: 21059851]  [MGI Ref ID J:166671]

Zhang J; Lee EY; Liu Y; Berman SD; Lodish HF; Lees JA. 2010. pRB and E2F4 play distinct cell-intrinsic roles in fetal erythropoiesis. Cell Cycle 9(2):371-6. [PubMed: 20023434]  [MGI Ref ID J:172630]

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 or heterozygotes may be bred.

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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.

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