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   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 gross phenotype has been observed in these mice, as yet. This strain may be useful in studies of development and cancer.

Development
A targeting vector was used to replace a 3' region of exon 1 and a 2.3 kb downstream intron sequence with PGK-neo 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. The strain has been maintained on a mixed C57BL/6 and 129S2/SvPas background by the donating laboratory.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Rbl1^tm1Tyj/Rbl1⁺

        involves: 129S2/SvPas * C57BL/6

• normal phenotype
• no abnormal phenotype detected
  • heterozygotes are viable and fertile; no increased morbidity or mortality is observed up to 24 months of age   (MGI Ref ID J:34058)

Rbl1^tm1Tyj/Rbl1^tm1Tyj

        involves: 129S2/SvPas * C57BL/6

• normal phenotype
• no abnormal phenotype detected
  • homozygotes are viable, fertile, and display no developmental or pathological defects at 4-12 months of age   (MGI Ref ID J:34058)
  • neither tumors nor increased morbidity or mortality are observed up to 24 months of age   (MGI Ref ID J:34058)
• cellular phenotype
• *normal* cellular phenotype
  • mutant embryonic fibroblasts (passage 4-6) derived from 12.5-day-old homozygotes exhibit normal cell cycle characteristics relative to wild-type cells   (MGI Ref ID J:34058)
• integument phenotype
• *normal* integument phenotype
  • newborn homozygotes display normal epidermal terminal differentiation relative to heterozygous mutant littermates   (MGI Ref ID J:82802)

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

Rbl1^tm1Tyj/Rbl1^tm1Tyj

        129/Sv

• skeleton phenotype
• increased diameter of long bones
  • on an inbred 129/Sv genetic background, homozygotes display no overt abnormalities up to 10 months of age; however, close examination reveals subtle thickening of the bones of the forelimbs   (MGI Ref ID J:34725)

View Research Applications

Research Applications

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

Cancer Research

Developmental Biology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Rbl1tm1Tyj
Allele Name		targeted mutation 1, Tyler Jacks
Allele Type		Targeted (knock-out)
Common Name(s)		p107-;
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		Rbl1, retinoblastoma-like 1 (p107)
Chromosome		2
Gene Common Name(s)		AW547426; CP107; PRB1; expressed sequence AW547426; p107;
Molecular Note		A PGK-neomycin cassette replaced sequences in exon 1 and a downstream intron of the Rbl1 gene. The authors predict that the mutant allele will synthesize only the first 22 amino acids of the wild-type protein. RBL1 protein was not detected in embryonic fibroblasts derived from homozygous mutant mice, or in homozygous mutant E18 embryos. Rbl1 transcript was not detected in homozygous mutant E18 embryos. [MGI Ref ID J:34058]

Genotyping

Genotyping Information

Genotyping Protocols

Rbl1^Tm1Tyj, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lee MH; Williams BO; Mulligan G; Mukai S; Bronson RT; Dyson N; Harlow E; Jacks T. 1996. Targeted disruption of p107: functional overlap between p107 and Rb. Genes Dev 10(13):1621-32. [PubMed: 8682293]  [MGI Ref ID J:34058]

Additional References

Rbl1^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]

Berman SD; West JC; Danielian PS; Caron AM; Stone JR; Lees JA. 2009. Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects. Proc Natl Acad Sci U S A 106(35):14932-6. [PubMed: 19706423]  [MGI Ref ID J:153091]

Brennan RC; Federico S; Bradley C; Zhang J; Flores-Otero J; Wilson M; Stewart C; Zhu F; Guy K; Dyer MA. 2011. Targeting the p53 Pathway in Retinoblastoma with Subconjunctival Nutlin-3a. Cancer Res 71(12):4205-13. [PubMed: 21515735]  [MGI Ref ID J:173754]

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]

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]

Conkrite K; Sundby M; Mu D; Mukai S; MacPherson D. 2012. Cooperation between Rb and Arf in suppressing mouse retinoblastoma. J Clin Invest 122(5):1726-33. [PubMed: 22484813]  [MGI Ref ID J:184538]

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]

Donovan SL; Schweers B; Martins R; Johnson D; Dyer MA. 2006. Compensation by tumor suppressor genes during retinal development in mice and humans. BMC Biol 4:14. [PubMed: 16672052]  [MGI Ref ID J:110865]

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]

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]

Jiang Z; Deng T; Jones R; Li H; Herschkowitz JI; Liu JC; Weigman VJ; Tsao MS; Lane TF; Perou CM; Zacksenhaus E. 2010. Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. J Clin Invest 120(9):3296-309. [PubMed: 20679727]  [MGI Ref ID J:165289]

Johnson DA; Zhang J; Frase S; Wilson M; Rodriguez-Galindo C; Dyer MA. 2007. Neuronal differentiation and synaptogenesis in retinoblastoma. Cancer Res 67(6):2701-11. [PubMed: 17363591]  [MGI Ref ID J:120315]

Lambertz I; Nittner D; Mestdagh P; Denecker G; Vandesompele J; Dyer MA; Marine JC. 2010. Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo. Cell Death Differ 17(4):633-41. [PubMed: 20019750]  [MGI Ref ID J:171794]

Laurie N; Mohan A; McEvoy J; Reed D; Zhang J; Schweers B; Ajioka I; Valentine V; Johnson D; Ellison D; Dyer MA. 2009. Changes in retinoblastoma cell adhesion associated with optic nerve invasion. Mol Cell Biol 29(23):6268-82. [PubMed: 19786571]  [MGI Ref ID J:154999]

Laurie NA; Donovan SL; Shih CS; Zhang J; Mills N; Fuller C; Teunisse A; Lam S; Ramos Y; Mohan A; Johnson D; Wilson M; Rodriguez-Galindo C; Quarto M; Francoz S; Mendrysa SM; Guy RK; Marine JC; Jochemsen AG; Dyer MA. 2006. Inactivation of the p53 pathway in retinoblastoma. Nature 444(7115):61-6. [PubMed: 17080083]  [MGI Ref ID J:115580]

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]

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; 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]

Nittner D; Lambertz I; Clermont F; Mestdagh P; Kohler C; Nielsen SJ; Jochemsen A; Speleman F; Vandesompele J; Dyer MA; Schramm A; Schulte JH; Marine JC. 2012. Synthetic lethality between Rb, p53 and Dicer or miR-17-92 in retinal progenitors suppresses retinoblastoma formation. Nat Cell Biol 14(9):958-65. [PubMed: 22864477]  [MGI Ref ID J:193515]

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]

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]

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]

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; Kobbert C; Bauer F; Skaletz-Rorowski A; Hohage H; Plenz G; Breithardt G; March KL. 2003. Vascular ligation response is independent of p107: stressing the role of the related p130. Am J Physiol Heart Circ Physiol 285(2):H915-8. [PubMed: 12860570]  [MGI Ref ID J:108045]

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]

Wang Y; Ray SK; Hinds PW; Leiter AB. 2007. The retinoblastoma protein, RB, is required for gastrointestinal endocrine cells to exit the cell cycle, but not for hormone expression. Dev Biol 311(2):478-86. [PubMed: 17936268]  [MGI Ref ID J:127522]

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]

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]

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]

Zhang J; Schweers B; Dyer MA. 2004. The first knockout mouse model of retinoblastoma. Cell Cycle 3(7):952-9. [PubMed: 15190215]  [MGI Ref ID J:103618]

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, heterozygotes or homozygotes 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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