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Strain Name:

C3Ou.129S2-Rb1tm1Tyj/J

Stock Number:

002546

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Genes & Alleles   Rb1;   Rb1tm1Tyj;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Targeted Mutation
Specieslaboratory mouse
Background Strain C3H/HeOuJ
Donor Strain B6,129S-Rb1tm1Tyj (129S2 derived D3 ES cell line)
Donating Investigator IMR Colony,   The Jackson Laboratory
GenerationN10F2

Strain 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.

Strain 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 to C3H/HeOuJ. As of February 1996 this strain had been backcrossed five times (N5). In 1999 it had been backcrossed to C3H/HeOuJ for 10 generations.

Mammalian Phenotype Terms assigned by genotype

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

Rb1tm1Tyj/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

Rb1tm1Tyj/Rb1tm1Tyj

        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 placental 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)

Rb1tm1Tyj/Rb1tm1Tyj

        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

Gene & Allele Details

Allele Symbol Rb1tm1Tyj
Allele Name targeted mutation 1, Tyler Jacks
Common Name(s) Rb-; Rbx3t; pRb-;
Mutation Made By Tyler Jacks,   Massachusetts Institute of Technology
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/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]

Control Information

  Allele   Control
 Rb1tm1Tyj  Wild-type from the colony
 Rb1tm1Tyj  000635 C3H/HeOuJ
 
  Considerations for Choosing Controls

Genotyping Protocols

Rb1tm1Tyj

Colony Maintenance

Breeding & HusbandryThe Rb1tm1Tyj strain is maintained by mating heterozygous mice to normal wildtype siblings. Heterozygous mice and normal wildtype siblings may be ordered.

Related Strains

Strains carrying   Rb1tm1Tyj allele
002082   129S-Rb1tm1Tyj/J
002102   B6.129S2-Rb1tm1Tyj/J
002900   FVB.129S2(B6)-Rb1tm1Tyj/J
View Strains carrying   Rb1tm1Tyj     (3 strains)

Additional Web Information

Congenic Nomenclature

Research Applications

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

Rb1tm1Tyj 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

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

Price and Supply Information

Strain Name: C3Ou.129S2-Rb1tm1Tyj/J
Stock Number: 002546

Price Details

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Supply Details

Standard SupplyRepository-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; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.

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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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