Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6J Donor Strain 129S2 via D3 ES cell line Generation N6F3   Donating Investigator IMR Colony,   The Jackson Laboratory

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for this targeted mutation die in utero, apparently from a failure to produce erythrocytes in the liver, demonstrating that the endogenous gene is essential for normal development. Heterozygous mice, which are analogous to human carrier individuals, do not develop retinal tumors, but do develop pituitary tumors by 8 months of age.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for this strain. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
This mutant strain was developed in the laboratory of Dr. Tyler Jacks at the Center for Cancer Research at the Massachusetts Institute of Technology. The 129-derived D3 ES cell line was used. This strain was made by backcrossing mutant mice at least 5 generations to C57BL/6J.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Rb1^tm1Tyj allele

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

View Strains carrying   Rb1^tm1Tyj     (3 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Rb1^tm1Tyj/Rb1⁺

        involves: 129S2/SvPas * C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:81082)
  • all heterozygous mutant mice die between 8.5 and 13.9 months of age
• tumorigenesis
• *normal* tumorigenesis (MGI Ref ID J:2511)
  • up to 11 months of age, none of >100 heterozygotes studied show any macroscopic sign of retinoblastoma relative to wild-type mice
  • in addition, no precursor lesions (retinomas) are detected by indirect ophthalmology or histological evaluation
• increased tumor incidence (MGI Ref ID J:2511)
  • at autopsy, heterozygotes with severe wasting symptoms show large pituitary adenocarcinomas (~ 6 mm in diameter)
  • consistent with the "two-hit" model proposed by Knudson, such pituitary tumors are shown to arise from cells in which the wild-type allele is absent
  • heterozygotes develop intermediate lobe pituitary tumors and 23/27 show c-cell thyroid tumors
• growth/size phenotype
• cachexia (MGI Ref ID J:2511)
  • at 8-10 months of age, a number of heterozygotes display severe wasting

Rb1^tm1Tyj/Rb1^tm1Tyj

        involves: 129S2/SvPas

• lethality-prenatal/perinatal
• lethality throughout fetal growth and development (MGI Ref ID J:105548)
  • live homozygotes are rarely recovered at E15.5 and never at E16.5
• hematopoietic system phenotype
• abnormal erythropoiesis (MGI Ref ID J:105548)
  • significant decrease in the percentage of enucleated erythrocytes, indicating defective erythrocyte maturation
• abnormal macrophage differentiation (MGI Ref ID J:105548)
  • fetal liver macrophages exhibit defects in differentiation, as indicated by small size, lack of extensive cytoplasmic projections, and weak staining for a mature macrophage marker
• impaired hematopoiesis (MGI Ref ID J:81643)
  • at E13.5, peripheral blood smears contain predominantly nucleated erythrocytes
• liver/biliary system phenotype
• liver hypoplasia (MGI Ref ID J:81643)
  • at E13.5 liver cellularity is decreased and the level of apoptosis is increased
• nervous system phenotype
• abnormal dorsal root ganglion morphology (MGI Ref ID J:105548)
  • detect ectopic mitosis and apoptosis in the dorsal root ganglia
• abnormal fourth ventricle morphology (MGI Ref ID J:105548)
  • detect ectopic mitosis and apoptosis in the intermediate zones of the fourth ventricle
• abnormal neurogenesis (MGI Ref ID J:81643)
  • at E13.5, proliferation is increased in the brain, dorsal root ganglia, and trigeminal ganglia
• abnormal third ventricle morphology (MGI Ref ID J:105548)
  • detect ectopic mitosis and apoptosis in the intermediate zones of the third ventricle
• abnormal trigeminal ganglion morphology (MGI Ref ID J:105548)
  • detect ectopic mitosis and apoptosis in the trigeminal ganglia
• increased neuron apoptosis (MGI Ref ID J:81643)
  • at E13.5, apoptosis is increased in the brain, dorsal root ganglia, and trigeminal ganglia
• vision/eye phenotype
• abnormal lens development (MGI Ref ID J:81643)
  • at E13.5, ectopic proliferating cells are seen in the interior of the lens and increased apoptosis is seen
• abnormal lens fiber morphology (MGI Ref ID J:105548)
  • detect ectopic mitoses in the lens fiber compartment that is not seen in wild-type
  • lens fiber cells are disorganized
• increased lens fiber apoptosis (MGI Ref ID J:105548)
  • apoptosis is detected in the lens fiber compartment that is not seen in wild-type
• homeostasis/metabolism phenotype
• hypoxia (MGI Ref ID J:81643)
  • expression of hypoxia-inducible genes is increased in the central nervous system at E13.5
• cellular phenotype
• abnormal cell cycle (MGI Ref ID J:105548)
  • MEFs exhibit an increase in the fraction of cells in the S and G2/M phases of the cell cycle
• abnormal cell cycle checkpoint function (MGI Ref ID J:105548)
  • MEFs fail to efficiently trigger G1/S cell cycle arrest in response to DNA damage
• increased cell proliferation (MGI Ref ID J:105548)
  • MEFs cultured at confluence exhibit an increase in cell proliferation compared to wild-type MEFs
• embryogenesis phenotype
• abnormal placenta labyrinth morphology (MGI Ref ID J:105548)
  • normal labyrinth architecture is disrupted
  • the porous appearance of the labyrinth layer is absent
• abnormal placental transport (MGI Ref ID J:105548)
  • exhibit defective placental transport as indicated by a 7.2% reduction of the essential fatty acid linoleic acid, arachidonic acid and docosahexaenoic acid in E14.5 embryos relative to wild-type
• reduced embryo size (MGI Ref ID J:105548)
• growth/size phenotype
• reduced embryo size (MGI Ref ID J:105548)
• immune system phenotype
• abnormal macrophage differentiation (MGI Ref ID J:105548)
  • fetal liver macrophages exhibit defects in differentiation, as indicated by small size, lack of extensive cytoplasmic projections, and weak staining for a mature macrophage marker
• skin/coat/nails phenotype
• pallor (MGI Ref ID J:105548)

Rb1^tm1Tyj/Rb1^tm1Tyj

        involves: 129S2/SvPas * C57BL/6

• lethality-prenatal/perinatal
• lethality throughout fetal growth and development (MGI Ref ID J:81082)
  • homozygous mutant embryos die between E14.5 and E15.5
• hematopoietic system phenotype
• abnormal erythropoiesis (MGI Ref ID J:2511)
  • at E13.5, homozygotes display impaired definitive erythropoiesis and fail to produce sufficient numbers of mature erythrocytes, resulting in hypoxia and eventually death
• abnormal erythrocyte morphology (MGI Ref ID J:2511)
  • in vitro, mutant erythroid precursors fail to reach end-stage differentiation: small hemaglobinized colonies from mutant mice are pale and contain increased numbers of small late normoblast-like cells instead of enucleated (mature) erythrocytes
  • similarly, mutant large erythroid colonies are pale, with <5% enucleated erythrocytes relative to wild-type (45%)
• low mean erythrocyte cell number (MGI Ref ID J:2511)
  • at E13.5, wild-type embryos contain on average 45% enucleated, definitive erythrocytes; in contrast, mutant embryos only contain 6.8% enucleated cells
• anemia (MGI Ref ID J:2511)
  • at E13.5, homozygotes are severely pale relative to wild-type embryos
• liver/biliary system phenotype
• abnormal liver morphology (MGI Ref ID J:2511)
  • at E13.5, mutant livers appear lacy and largely acellular; in contrast, wild-type livers are densely packed with cells (90% of which are of erythroid lineage)
• small liver (MGI Ref ID J:2511)
  • at E13.5, homozygotes display a slight reduction in liver size
• homeostasis/metabolism phenotype
• pericardial edema (MGI Ref ID J:2511)
  • at E13.5, homozygotes display significant edema, particularly in the pericardial space
• skin edema (MGI Ref ID J:2511)
  • at E13.5, edema results in damage of the dermis and underlying mesenchyme
  • however, most non-hematopoietic tissues remain unaffected until death (~E14.5)
• cardiovascular system phenotype
• pericardial edema (MGI Ref ID J:2511)
  • at E13.5, homozygotes display significant edema, particularly in the pericardial space
• skin/coat/nails phenotype
• skin edema (MGI Ref ID J:2511)
  • at E13.5, edema results in damage of the dermis and underlying mesenchyme
  • however, most non-hematopoietic tissues remain unaffected until death (~E14.5)
• nervous system phenotype
• increased neuron apoptosis (MGI Ref ID J:2511)
  • at E12.5, mutant embryos exhibit increased neuronal apoptosis in the spinal cord, dorsal root ganglia and parts of the hindbrain
  • neuronal cell death occurs prior to the manifestation of the erythropoietic defect, and does not appear to be a secondary effect of anemia-induced hypoxia
• vision/eye phenotype
• *normal* vision/eye phenotype (MGI Ref ID J:2511)
  • at 13.5 dpc, homozygotes display normal retinal development at E13.5, homozygotes display normal retinal development
• cellular phenotype
• increased apoptosis (MGI Ref ID J:37145)
  • at E13.5, TUNEL analysis indicates a significant increase in apoptotic nuclei throughout the mutant nervous system (esp. dorsal ganglia), in skeletal muscle precursor cells (e.g. tongue myoblasts), lens, and to a lesser extent in liver
  • in contrast, no significant increase in apoptosis is noted in the mutant lung or cardiac muscles
• increased cell proliferation (MGI Ref ID J:81082)
  • MEFs largely fail to arrest in response to confluent growth and ~40% of the cells enter S phase
• behavior/neurological phenotype
• hunched posture (MGI Ref ID J:37145)
  • at E13.5, 7 of 8 homozygotes display a hunchback posture
• skeleton phenotype
• abnormal cartilage morphology (MGI Ref ID J:37145)
  • at E13.5, 7 of 8 homozygotes display a reduced cartilaginous frame (perichondrium) relative to wild-type mice

View Research Applications

Research Applications

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

Rb1^tm1Tyj related

Apoptosis Research
Endogenous Regulators

Cancer Research
Increased Tumor Incidence (Other Tissues/Organs: pituitary)
Tumor Suppressor Genes (pituitary tumors)

Developmental Biology Research
Internal/Organ Defects (liver)

Hematological Research
Hematopoietic Defects

Immunology and Inflammation Research
Intracellular Signaling Molecules

Internal/Organ Research
Liver Defects

Mouse/Human Gene Homologs
retinoblastoma

Genes & Alleles

Gene & Allele Information

Allele Symbol		Rb1tm1Tyj
Allele Name		targeted mutation 1, Tyler Jacks
Allele Type		Targeted (knock-out)
Common Name(s)		Rb-; Rbx3t; pRb-;
Mutation Made By		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		Rb1, retinoblastoma 1
Chromosome		14
Gene Common Name(s)		OSRC; RB; Rb-1; p105-Rb; pRb; pp110;
General Note		This is one of several targeted null mutations of Rb1 that have been created. Results appear to be similar for all the mutations (J:2498, J:2511, J:2516). Heterozygotes for the mutations show no predisposition to retinoblastoma. Homozygotes die in utero with neuronal and hematopoietic system abnormalities. Transfer of a human RB1 mini-transgene into the mutant mice corrects the defects (J:2516). On the other hand, transfer of the human gene into mice with a normal Rb1 genotype, causing overexpression of the gene product, produces mice dwarfed in proportion to the number of extra RB1 copies they carry (J:15042).Homozygous Rb1tm1Tyj mutant mice given a transgene producing low levels of Rb1 product survive to birth, but die at that stage due tofailure of myogenesis. Myoblasts undergo massive apoptosis, and surviving cells do not undergo terminal differentiation (J:37145).
Molecular Note		A PGK-neomycin resistance cassette replaced part of intron 3 and introduced three nucleotide changes into exon 3, creating two termination codons and a new PstI site. The authors predict translation of a truncated protein by the mutant allele. Immunoblotanalysis of E12.5 brain did not detect full length RB1 protein in homozygous mice. [MGI Ref ID J:2511]

Genotyping

Genotyping Information

Genotyping Protocols

NEOTD (Generic Neo), STD PCR, vers. 1
Rb1^tm1Tyj, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Jacks T; Fazeli A; Schmitt EM; Bronson RT; Goodell MA; Weinberg RA. 1992. Effects of an Rb mutation in the mouse [see comments] Nature 359(6393):295-300. [PubMed: 1406933]  [MGI Ref ID J:2511]

Additional References

Eason DD; LeBron C; Coppola D; Moscinski LC; Livingston S; Sutton ET; Blanck G. 2003. Development of CD30+ lymphoproliferative disease in mice lacking interferon regulatory factor-1. Oncogene 22(40):6166-76. [PubMed: 13679855]  [MGI Ref ID J:85972]

Macleod KF; Hu Y; Jacks T. 1996. Loss of Rb activates both p53-dependent and independent cell death pathways in the developing mouse nervous system. EMBO J 15(22):6178-88. [PubMed: 8947040]  [MGI Ref ID J:37025]

Novitch BG; Mulligan GJ; Jacks T; Lassar AB. 1996. Skeletal muscle cells lacking the retinoblastoma protein display defects in muscle gene expression and accumulate in S and G2 phases of the cell cycle. J Cell Biol 135(2):441-56. [PubMed: 8896600]  [MGI Ref ID J:36067]

Simpson MT; MacLaurin JG; Xu D; Ferguson KL; Vanderluit JL; Davoli MA; Roy S; Nicholson DW; Robertson GS; Park DS; Slack RS. 2001. Caspase 3 deficiency rescues peripheral nervous system defect in retinoblastoma nullizygous mice. J Neurosci 21(18):7089-98. [PubMed: 11549719]  [MGI Ref ID J:71535]

Rb1^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]

Andreu-Vieyra C; Chen R; Matzuk MM. 2008. Conditional deletion of the retinoblastoma (rb) gene in ovarian granulosa cells leads to premature ovarian failure. Mol Endocrinol 22(9):2141-61. [PubMed: 18599617]  [MGI Ref ID J:138319]

Andreu-Vieyra C; Chen R; Matzuk MM. 2007. Effects of granulosa cell-specific deletion of Rb in Inha-alpha null female mice. Endocrinology 148(8):3837-49. [PubMed: 17510234]  [MGI Ref ID J:123844]

Bajenaru ML; Donahoe J; Corral T; Reilly KM; Brophy S; Pellicer A; Gutmann DH. 2001. Neurofibromatosis 1 (NF1) heterozygosity results in a cell-autonomous growth advantage for astrocytes. Glia 33(4):314-23. [PubMed: 11246230]  [MGI Ref ID J:80411]

Bakkar N; Wang J; Ladner KJ; Wang H; Dahlman JM; Carathers M; Acharyya S; Rudnicki MA; Hollenbach AD; Guttridge DC. 2008. IKK/NF-kappaB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis. J Cell Biol 180(4):787-802. [PubMed: 18299349]  [MGI Ref ID J:135692]

Bignon YJ; Chen Y; Chang CY; Riley DJ; Windle JJ; Mellon PL; Lee WH. 1993. Expression of a retinoblastoma transgene results in dwarf mice. Genes Dev 7(9):1654-62. [PubMed: 8370518]  [MGI Ref ID J:15042]

Borges HL; Hunton IC; Wang JY. 2007. Reduction of apoptosis in Rb-deficient embryos via Abl knockout. Oncogene 26(26):3868-77. [PubMed: 17173068]  [MGI Ref ID J:122882]

Bultman SJ; Herschkowitz JI; Godfrey V; Gebuhr TC; Yaniv M; Perou CM; Magnuson T. 2008. Characterization of mammary tumors from Brg1 heterozygous mice. Oncogene 27(4):460-8. [PubMed: 17637742]  [MGI Ref ID J:132091]

Chesnokova V; Kovacs K; Castro AV; Zonis S; Melmed S. 2005. Pituitary hypoplasia in Pttg-/- mice is protective for Rb+/- pituitary tumorigenesis. Mol Endocrinol 19(9):2371-9. [PubMed: 15919720]  [MGI Ref ID J:114916]

Chesnokova V; Zonis S; Rubinek T; Yu R; Ben-Shlomo A; Kovacs K; Wawrowsky K; Melmed S. 2007. Senescence mediates pituitary hypoplasia and restrains pituitary tumor growth. Cancer Res 67(21):10564-72. [PubMed: 17975001]  [MGI Ref ID J:127141]

Choi YS; Lee JE; Cheong C; Sung YH; Yang EY; Park CB; Song J; Park SC; Lee HW. 2005. Generation of reversible Rb-knockdown mice. Mech Ageing Dev 126(11):1164-9. [PubMed: 16087217]  [MGI Ref ID J:101661]

Clark AJ; Doyle KM; Humbert PO. 2004. Cell-intrinsic requirement for pRb in erythropoiesis. Blood 104(5):1324-6. [PubMed: 15155463]  [MGI Ref ID J:92702]

Clarke AR; Maandag ER; van Roon M; van der Lugt NM; van der Valk M; Hooper ML; Berns A; te Riele H. 1992. Requirement for a functional Rb-1 gene in murine development [see comments] Nature 359(6393):328-30. [PubMed: 1406937]  [MGI Ref ID J:2498]

Coxon AB; Ward JM; Geradts J; Otterson GA; Zajac-Kaye M; Kaye FJ. 1998. RET cooperates with RB/p53 inactivation in a somatic multi-step model for murine thyroid cancer. Oncogene 17(12):1625-8. [PubMed: 9794240]  [MGI Ref ID J:50139]

Davis JN; McCabe MT; Hayward SW; Park JM; Day ML. 2005. Disruption of Rb/E2F pathway results in increased cyclooxygenase-2 expression and activity in prostate epithelial cells. Cancer Res 65(9):3633-42. [PubMed: 15867358]  [MGI Ref ID J:98347]

De Bruin A; Wu L; Saavedra HI; Wilson P; Yang Y; Rosol TJ; Weinstein M; Robinson ML; Leone G. 2003. Rb function in extraembryonic lineages suppresses apoptosis in the CNS of Rb-deficient mice. Proc Natl Acad Sci U S A 100(11):6546-51. [PubMed: 12732721]  [MGI Ref ID J:83621]

Dirlam A; Spike BT; Macleod KF. 2007. Deregulated E2f-2 underlies cell cycle and maturation defects in retinoblastoma null erythroblasts. Mol Cell Biol 27(24):8713-28. [PubMed: 17923680]  [MGI Ref ID J:129010]

Donangelo I; Gutman S; Horvath E; Kovacs K; Wawrowsky K; Mount M; Melmed S. 2006. Pituitary tumor transforming gene overexpression facilitates pituitary tumor development. Endocrinology 147(10):4781-91. [PubMed: 16809444]  [MGI Ref ID J:113662]

Donangelo I; Melmed S. 2005. Pathophysiology of pituitary adenomas. J Endocrinol Invest 28(11 Suppl):100-5. [PubMed: 16625857]  [MGI Ref ID J:116408]

Donovan SL; Dyer MA. 2004. Developmental defects in Rb-deficient retinae. Vision Res 44(28):3323-33. [PubMed: 15536000]  [MGI Ref ID J:102508]

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]

Eason DD; LeBron C; Coppola D; Moscinski LC; Livingston S; Sutton ET; Blanck G. 2003. Development of CD30+ lymphoproliferative disease in mice lacking interferon regulatory factor-1. Oncogene 22(40):6166-76. [PubMed: 13679855]  [MGI Ref ID J:85972]

Guidi CJ; Mudhasani R; Hoover K; Koff A; Leav I; Imbalzano AN; Jones SN. 2006. Functional interaction of the retinoblastoma and ini1/snf5 tumor suppressors in cell growth and pituitary tumorigenesis. Cancer Res 66(16):8076-82. [PubMed: 16912184]  [MGI Ref ID J:112109]

Guo Z; Yikang S; Yoshida H; Mak TW; Zacksenhaus E. 2001. Inactivation of the retinoblastoma tumor suppressor induces apoptosis protease-activating factor-1 dependent and independent apoptotic pathways during embryogenesis. Cancer Res 61(23):8395-400. [PubMed: 11731416]  [MGI Ref ID J:73154]

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]

Iavarone A; King ER; Dai XM; Leone G; Stanley ER; Lasorella A. 2004. Retinoblastoma promotes definitive erythropoiesis by repressing Id2 in fetal liver macrophages. Nature 432(7020):1040-5. [PubMed: 15616565]  [MGI Ref ID J:95106]

Jiang Z; Liang P; Leng R; Guo Z; Liu Y; Liu X; Bubnic S; Keating A; Murray D; Goss P; Zacksenhaus E. 2000. E2F1 and p53 are dispensable, whereas p21(Waf1/Cip1) cooperates with Rb to restrict endoreduplication and apoptosis during skeletal myogenesis Dev Biol 227(1):28-41. [PubMed: 11076674]  [MGI Ref ID J:65679]

Jiang Z; Zacksenhaus E; Gallie BL; Phillips RA. 1997. The retinoblastoma gene family is differentially expressed during embryogenesis. Oncogene 14(15):1789-97. [PubMed: 9150384]  [MGI Ref ID J:39767]

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]

Kalitsis P; Fowler KJ; Griffiths B; Earle E; Chow CW; Jamsen K; Choo KH. 2005. Increased chromosome instability but not cancer predisposition in haploinsufficient Bub3 mice. Genes Chromosomes Cancer 44(1):29-36. [PubMed: 15898111]  [MGI Ref ID J:99580]

Keramaris E; Ruzhynsky VA; Callaghan SM; Wong E; Davis RJ; Flavell R; Slack RS; Park DS. 2008. Required roles of Bax and JNKs in central and peripheral nervous system death of retinoblastoma-deficient mice. J Biol Chem 283(1):405-15. [PubMed: 17984095]  [MGI Ref ID J:130256]

Knostman KA; Jhiang SM; Capen CC. 2007. Genetic alterations in thyroid cancer: the role of mouse models. Vet Pathol 44(1):1-14. [PubMed: 17197619]  [MGI Ref ID J:129329]

Lasorella A; Noseda M; Beyna M; Yokota Y; Iavarone A. 2000. Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins. Nature 407(6804):592-8. [PubMed: 11034201]  [MGI Ref ID J:77276]

Lasorella A; Rothschild G; Yokota Y; Russell RG; Iavarone A. 2005. Id2 mediates tumor initiation, proliferation, and angiogenesis in rb mutant mice. Mol Cell Biol 25(9):3563-74. [PubMed: 15831462]  [MGI Ref ID J:97629]

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]

Lee EY; Cam H; Ziebold U; Rayman JB; Lees JA; Dynlacht BD. 2002. E2F4 loss suppresses tumorigenesis in Rb mutant mice. Cancer Cell 2(6):463-72. [PubMed: 12498715]  [MGI Ref ID J:81082]

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]

Leung SW; Wloga EH; Castro AF; Nguyen T; Bronson RT; Yamasaki L. 2004. A dynamic switch in Rb+/- mediated neuroendocrine tumorigenesis. Oncogene 23(19):3296-307. [PubMed: 15021915]  [MGI Ref ID J:89741]

Liu Y; Zacksenhaus E. 2000. E2F1 mediates ectopic proliferation and stage-specific p53-dependent apoptosis but not aberrant differentiation in the ocular lens of Rb deficient fetuses. Oncogene 19(52):6065-73. [PubMed: 11146559]  [MGI Ref ID J:66392]

Macleod KF; Hu Y; Jacks T. 1996. Loss of Rb activates both p53-dependent and independent cell death pathways in the developing mouse nervous system. EMBO J 15(22):6178-88. [PubMed: 8947040]  [MGI Ref ID J:37025]

Mantela J; Jiang Z; Ylikoski J; Fritzsch B; Zacksenhaus E; Pirvola U. 2005. The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear. Development 132(10):2377-88. [PubMed: 15843406]  [MGI Ref ID J:98518]

Matoso A; Zhou Z; Hayama R; Flesken-Nikitin A; Nikitin AY. 2008. Cell lineage-specific interactions between Men1 and Rb in neuroendocrine neoplasia. Carcinogenesis 29(3):620-8. [PubMed: 17893233]  [MGI Ref ID J:133299]

Morgenbesser SD; Williams BO; Jacks T; DePinho RA. 1994. p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens [see comments] Nature 371(6492):72-4. [PubMed: 8072529]  [MGI Ref ID J:19995]

Novitch BG; Spicer DB; Kim PS; Cheung WL; Lassar AB. 1999. pRb is required for MEF2-dependent gene expression as well as cell-cycle arrest during skeletal muscle differentiation. Curr Biol 9(9):449-59. [PubMed: 10322110]  [MGI Ref ID J:54605]

Reimann M; Loddenkemper C; Rudolph C; Schildhauer I; Teichmann B; Stein H; Schlegelberger B; Dorken B; Schmitt CA. 2007. The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo. Blood 110(8):2996-3004. [PubMed: 17562874]  [MGI Ref ID J:125810]

Schmitt CA; McCurrach ME; de Stanchina E; Wallace-Brodeur RR; Lowe SW. 1999. INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53. Genes Dev 13(20):2670-7. [PubMed: 10541553]  [MGI Ref ID J:58293]

Schmitt CA; Wallace-Brodeur RR; Rosenthal CT; McCurrach ME; Lowe SW. 2000. DNA damage responses and chemosensitivity in the E mu-myc mouse lymphoma model. Cold Spring Harb Symp Quant Biol 65:499-510. [PubMed: 12760067]  [MGI Ref ID J:84207]

Serra R; Moses HL. 1995. pRb is necessary for inhibition of N-myc expression by TGF-beta 1 in embryonic lung organ cultures. Development 121(9):3057-66. [PubMed: 7555731]  [MGI Ref ID J:28703]

Simpson MT; MacLaurin JG; Xu D; Ferguson KL; Vanderluit JL; Davoli MA; Roy S; Nicholson DW; Robertson GS; Park DS; Slack RS. 2001. Caspase 3 deficiency rescues peripheral nervous system defect in retinoblastoma nullizygous mice. J Neurosci 21(18):7089-98. [PubMed: 11549719]  [MGI Ref ID J:71535]

Spike BT; Dibling BC; Macleod KF. 2007. Hypoxic stress underlies defects in erythroblast islands in the Rb-null mouse. Blood 110(6):2173-81. [PubMed: 17557897]  [MGI Ref ID J:127220]

Spike BT; Dirlam A; Dibling BC; Marvin J; Williams BO; Jacks T; Macleod KF. 2004. The Rb tumor suppressor is required for stress erythropoiesis. EMBO J 23(21):4319-29. [PubMed: 15457215]  [MGI Ref ID J:93304]

Sun H; Chang Y; Schweers B; Dyer MA; Zhang X; Hayward SW; Goodrich DW. 2006. An E2F binding-deficient Rb1 protein partially rescues developmental defects associated with Rb1 nullizygosity. Mol Cell Biol 26(4):1527-37. [PubMed: 16449662]  [MGI Ref ID J:105548]

Takahashi C; Bronson RT; Socolovsky M; Contreras B; Lee KY; Jacks T; Noda M; Kucherlapati R; Ewen ME. 2003. Rb and N-ras function together to control differentiation in the mouse. Mol Cell Biol 23(15):5256-68. [PubMed: 12861012]  [MGI Ref ID J:84571]

Takahashi C; Contreras B; Bronson RT; Loda M; Ewen ME. 2004. Genetic Interaction between Rb and K-ras in the Control of Differentiation and Tumor Suppression. Mol Cell Biol 24(23):10406-15. [PubMed: 15542848]  [MGI Ref ID J:94087]

Takahashi C; Contreras B; Iwanaga T; Takegami Y; Bakker A; Bronson RT; Noda M; Loda M; Hunt JL; Ewen ME. 2006. Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor. Nat Genet 38(1):118-23. [PubMed: 16369533]  [MGI Ref ID J:106133]

TeKippe M; Harrison DE; Chen J. 2003. Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. Exp Hematol 31(6):521-7. [PubMed: 12829028]  [MGI Ref ID J:115677]

Tracy K; Dibling BC; Spike BT; Knabb JR; Schumacker P; Macleod KF. 2007. BNIP3 is an RB/E2F target gene required for hypoxia-induced autophagy. Mol Cell Biol 27(17):6229-42. [PubMed: 17576813]  [MGI Ref ID J:125010]

Tsai KY; Hu Y; Macleod KF; Crowley D; Yamasaki L; Jacks T. 1998. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. Mol Cell 2(3):293-304. [PubMed: 9774968]  [MGI Ref ID J:50085]

Tsai KY; MacPherson D; Rubinson DA; Crowley D; Jacks T. 2002. ARF is not required for apoptosis in Rb mutant mouse embryos. Curr Biol 12(2):159-63. [PubMed: 11818069]  [MGI Ref ID J:73917]

Tsai KY; MacPherson D; Rubinson DA; Nikitin AY; Bronson R; Mercer KL; Crowley D; Jacks T. 2002. ARF mutation accelerates pituitary tumor development in Rb+/- mice. Proc Natl Acad Sci U S A 99(26):16865-70. [PubMed: 12486224]  [MGI Ref ID J:81016]

Vanderluit JL; Ferguson KL; Nikoletopoulou V; Parker M; Ruzhynsky V; Alexson T; McNamara SM; Park DS; Rudnicki M; Slack RS. 2004. p107 regulates neural precursor cells in the mammalian brain. J Cell Biol 166(6):853-63. [PubMed: 15353549]  [MGI Ref ID J:92520]

Vasavada RC; Cozar-Castellano I; Sipula D; Stewart AF. 2007. Tissue-specific deletion of the retinoblastoma protein in the pancreatic beta-cell has limited effects on beta-cell replication, mass, and function. Diabetes 56(1):57-64. [PubMed: 17192465]  [MGI Ref ID J:121935]

Wang Y; Hayward SW; Donjacour AA; Young P; Jacks T; Sage J; Dahiya R; Cardiff RD; Day ML; Cunha GR. 2000. Sex hormone-induced carcinogenesis in Rb-deficient prostate tissue Cancer Res 60(21):6008-17. [PubMed: 11085521]  [MGI Ref ID J:66195]

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Wenzel PL; Wu L; de Bruin A; Chong JL; Chen WY; Dureska G; Sites E; Pan T; Sharma A; Huang K; Ridgway R; Mosaliganti K; Sharp R; Machiraju R; Saltz J; Yamamoto H; Cross JC; Robinson ML; Leone G. 2007. Rb is critical in a mammalian tissue stem cell population. Genes Dev 21(1):85-97. [PubMed: 17210791]  [MGI Ref ID J:117307]

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Wu L; de Bruin A; Saavedra HI; Starovic M; Trimboli A; Yang Y; Opavska J; Wilson P; Thompson JC; Ostrowski MC; Rosol TJ; Woollett LA; Weinstein M; Cross JC; Robinson ML; Leone G. 2003. Extra-embryonic function of Rb is essential for embryonic development and viability. Nature 421(6926):942-7. [PubMed: 12607001]  [MGI Ref ID J:82350]

Xiao H; Goodrich DW. 2005. The retinoblastoma tumor suppressor protein is required for efficient processing and repair of trapped topoisomerase II-DNA-cleavable complexes. Oncogene 24(55):8105-13. [PubMed: 16091739]  [MGI Ref ID J:104415]

Yamasaki L; Bronson R; Williams BO; Dyson NJ; Harlow E; Jacks T. 1998. Loss of E2F-1 reduces tumorigenesis and extends the lifespan of Rb1(+/-)mice. Nat Genet 18(4):360-4. [PubMed: 9537419]  [MGI Ref ID J:47108]

Yang H; Williams BO; Hinds PW; Shih TS; Jacks T; Bronson RT; Livingston DM. 2002. Tumor suppression by a severely truncated species of retinoblastoma protein. Mol Cell Biol 22(9):3103-10. [PubMed: 11940667]  [MGI Ref ID J:75738]

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Zhang J; Gray J; Wu L; Leone G; Rowan S; Cepko CL; Zhu X; Craft CM; Dyer MA. 2004. Rb regulates proliferation and rod photoreceptor development in the mouse retina. Nat Genet 36(4):351-60. [PubMed: 14991054]  [MGI Ref ID J:109491]

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Ziebold U; Lee EY; Bronson RT; Lees JA. 2003. E2F3 loss has opposing effects on different pRB-deficient tumors, resulting in suppression of pituitary tumors but metastasis of medullary thyroid carcinomas. Mol Cell Biol 23(18):6542-52. [PubMed: 12944480]  [MGI Ref ID J:85441]

Ziebold U; Reza T; Caron A; Lees JA. 2001. E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos. Genes Dev 15(4):386-91. [PubMed: 11230146]  [MGI Ref ID J:67783]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The Rb1tm1Tyj strain is maintained by mating heterozygous mice to normal wildtype siblings. Heterozygous mice and normal wildtype siblings may be ordered. Expected coat color from breeding:Black
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
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.

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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.

For additional 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

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.”

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.