Overview

Also Known As:Rb^x3t

These Rb1 knock-out mice exhibit neuronal cell death and defective erythropoiesis. They are suitable for use in applications related to the study of retinoblastoma.

Donating Investigator

IMR Colony, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Rb1^tm1Tyj

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Rb1	RB transcriptional corepressor 1

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Research Applications

Mouse/Human Gene Homologs
Cancer Research
Apoptosis Research
Hematological Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for this targeted mutation die in utero. Homozygous embryos are morphologically indistinguishable from normal embryos at 12.5 days post coitum, but then die between 13.5 d.p.c and 14.5 d.p.c. Defects are seen in fetal liver hematopoiesis as well as in lens and nervous system 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.

Control Suggestions

Wild-type from the colony
001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

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):295-300PubMed: 1406933 MGI: J:2511

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Genetics

Rb1^tm1Tyj

Allele Symbol: Rb1^tm1Tyj

Allele Name	targeted mutation 1, Tyler Jacks
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	pRb^-; Rb-; Rb^x3t; Rb1^-
Gene Symbol and Name	Rb1, RB transcriptional corepressor 1
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	14
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 Rb^1tm1Tyj mutant mice given a transgene producing low levels of Rb1 product survive to birth, but die at that stage due to failure 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. Immunoblot analysis of E12.5 brain did not detect full length RB1 protein in homozygous mice.
Mutations Made By	Dr. Tyler Jacks, Massachusetts Institute of Technology

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Rb1^tm1Tyj related

Mouse/Human Gene Homologs
- retinoblastoma
Cancer Research
- Tumor Suppressor Genes
  - pituitary tumors
- Increased Tumor Incidence
  - Other Tissues/Organs
  - Other Tissues/Organs: pituitary
Apoptosis Research
- Endogenous Regulators
Hematological Research
- Hematopoietic Defects
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
Internal/Organ Research
- Liver Defects
Developmental Biology Research
- Internal/Organ Defects
  - liver

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Rb1^tm1Tyj/Rb1^tm1Tyj
involves: 129S2/SvPas * C57BL/6

behavior/neurological phenotype

hunched posture
- at E13.5, 7 of 8 homozygotes display a hunchback posture

hematopoietic system phenotype

abnormal erythropoiesis
- at E13.5, homozygotes display impaired definitive erythropoiesis and fail to produce sufficient numbers of mature erythrocytes, resulting in hypoxia and eventually death

anemia
- at E13.5, homozygotes are severely pale relative to wild-type embryos

abnormal erythrocyte morphology
- 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
- at E13.5, wild-type embryos contain on average 45% enucleated, definitive erythrocytes; in contrast, mutant embryos only contain 6.8% enucleated cells

homeostasis/metabolism phenotype

skin edema
- however, most non-hematopoietic tissues remain unaffected until death (~E14.5)
- at E13.5, edema results in damage of the dermis and underlying mesenchyme

pericardial edema
- at E13.5, homozygotes display significant edema, particularly in the pericardial space

integument phenotype

skin edema
- at E13.5, edema results in damage of the dermis and underlying mesenchyme
- however, most non-hematopoietic tissues remain unaffected until death (~E14.5)

liver/biliary system phenotype

abnormal liver morphology
- 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
- at E13.5, homozygotes display a slight reduction in liver size

cardiovascular system phenotype

pericardial edema
- at E13.5, homozygotes display significant edema, particularly in the pericardial space

mammalian phenotype

nervous system phenotype
- Normal - normal numbers of primary neurospheres are produced from cultured E10 telencephalic neuroepithelia

vision/eye phenotype
- Normal - at E13.5, homozygotes display normal retinal development
- at 13.5 dpc, homozygotes display normal retinal development

mortality/aging

lethality throughout fetal growth and development, complete penetrance
- homozygous mutant embryos die between E14.5 and E15.5

nervous system phenotype

increased neuron apoptosis
- 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

skeleton phenotype

abnormal cartilage morphology
- at E13.5, 7 of 8 homozygotes display a reduced cartilaginous frame (perichondrium) relative to wild-type mice

cellular phenotype

increased neuron apoptosis
- 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

increased apoptosis
- 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
- Normal - in contrast, no significant increase in apoptosis is noted in the mutant lung or cardiac muscles

increased cell proliferation
- MEFs largely fail to arrest in response to confluent growth and ~40% of the cells enter S phase

Genotype: Rb1^tm1Tyj/Rb1^tm1Tyj
involves: 129S2/SvPas

growth/size/body region phenotype

decreased embryo size

hematopoietic system phenotype

abnormal erythropoiesis
- significant decrease in the percentage of enucleated erythrocytes, indicating defective erythrocyte maturation

abnormal macrophage differentiation
- 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

increased nucleated erythrocyte cell number
- at E13.5, peripheral blood smears contain predominantly nucleated erythrocytes

homeostasis/metabolism phenotype

hypoxia
- expression of hypoxia-inducible genes is increased in the central nervous system at E13.5

immune system phenotype

abnormal macrophage differentiation
- 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

integument phenotype

pallor

liver/biliary system phenotype

liver hypoplasia
- at E13.5 liver cellularity is decreased and the level of apoptosis is increased

mortality/aging

embryonic lethality during organogenesis, complete penetrance
- live homozygotes are rarely recovered at E15.5 and never at E16.5

nervous system phenotype

abnormal dorsal root ganglion morphology
- detect ectopic mitosis and apoptosis in the dorsal root ganglia

abnormal trigeminal ganglion morphology
- detect ectopic mitosis and apoptosis in the trigeminal ganglia

increased neuron apoptosis
- at E13.5, apoptosis is increased in the brain, dorsal root ganglia, and trigeminal ganglia

abnormal neuron differentiation
- at E13.5, proliferation is increased in the brain, dorsal root ganglia, and trigeminal ganglia

abnormal fourth ventricle morphology
- detect ectopic mitosis and apoptosis in the intermediate zones of the fourth ventricle

abnormal third ventricle morphology
- detect ectopic mitosis and apoptosis in the intermediate zones of the third ventricle

vision/eye phenotype

abnormal lens fiber morphology
- lens fiber cells are disorganized
- detect ectopic mitoses in the lens fiber compartment that is not seen in wild-type

abnormal lens development
- at E13.5, ectopic proliferating cells are seen in the interior of the lens and increased apoptosis is seen

increased lens fiber apoptosis
- apoptosis is detected in the lens fiber compartment that is not seen in wild-type

cellular phenotype

increased lens fiber apoptosis
- apoptosis is detected in the lens fiber compartment that is not seen in wild-type

increased neuron apoptosis
- at E13.5, apoptosis is increased in the brain, dorsal root ganglia, and trigeminal ganglia

abnormal macrophage differentiation
- 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

abnormal cell cycle checkpoint function
- MEFs fail to efficiently trigger G1/S cell cycle arrest in response to DNA damage

abnormal cell cycle
- MEFs exhibit an increase in the fraction of cells in the S and G2/M phases of the cell cycle

abnormal neuron differentiation
- at E13.5, proliferation is increased in the brain, dorsal root ganglia, and trigeminal ganglia

increased fibroblast proliferation
- MEFs cultured at confluence exhibit an increase in cell proliferation compared to wild-type MEFs

embryo phenotype

abnormal placenta labyrinth morphology
- normal labyrinth architecture is disrupted
- the porous appearance of the labyrinth layer is absent

abnormal placental transport
- 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

decreased embryo size

Genotype: Rb1^tm1Tyj/Rb1⁺
involves: 129S2/SvPas * C57BL/6J

nervous system phenotype

increased pituitary adenohypophysis tumor incidence
- Normal - however, no parathyroid adenomas are observed
- mice exhibit tumors of the pituitary anterior lobe (42%)

increased pituitary melanotroph tumor incidence
- all mice exhibit tumors of the pituitary intermediate lobe

respiratory system phenotype

increased lung tumor incidence
- in 60% of mice

endocrine/exocrine gland phenotype

increased pituitary adenohypophysis tumor incidence
- Normal - however, no parathyroid adenomas are observed
- mice exhibit tumors of the pituitary anterior lobe (42%)

increased pituitary melanotroph tumor incidence
- all mice exhibit tumors of the pituitary intermediate lobe

increased thyroid C-cell carcinoma incidence
- all mice exhibit metastic thyroid C-cell carcinomas

increased pheochromocytoma incidence
- in 40% of mice

mortality/aging

premature death
- median lifespan is 372 days compared to 546 days for Men1^tm1.1Ctre heterozygotes

neoplasm

increased lung tumor incidence
- in 60% of mice

increased metastatic potential
- 60% of mice exhibit lung metastasis

increased pheochromocytoma incidence
- in 40% of mice

increased thyroid C-cell carcinoma incidence
- all mice exhibit metastic thyroid C-cell carcinomas

increased pituitary adenohypophysis tumor incidence
- mice exhibit tumors of the pituitary anterior lobe (42%)
- Normal - however, no parathyroid adenomas are observed

increased pituitary melanotroph tumor incidence
- all mice exhibit tumors of the pituitary intermediate lobe

Genotype: Rb1^tm1Tyj/Rb1⁺
involves: 129S2/SvPas * C57BL/6

endocrine/exocrine gland phenotype

increased pituitary gland tumor incidence
- 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

increased thyroid tumor incidence
- 23/27 heterozygotes show c-cell thyroid tumors

nervous system phenotype

increased pituitary gland tumor incidence
- 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
- at autopsy, heterozygotes with severe wasting symptoms show large pituitary adenocarcinomas (~ 6 mm in diameter)

growth/size/body region phenotype

cachexia
- at 8-10 months of age, a number of heterozygotes display severe wasting

mammalian phenotype

neoplasm
- Normal - in addition, no precursor lesions (retinomas) are detected by indirect ophthalmology or histological evaluation
- Normal - up to 11 months of age, none of >100 heterozygotes studied show any macroscopic sign of retinoblastoma relative to wild-type mice

mortality/aging

premature death
- all heterozygous mutant mice die between 8.5 and 13.9 months of age

neoplasm

increased pituitary gland tumor incidence
- 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

increased thyroid tumor incidence
- 23/27 heterozygotes show c-cell thyroid tumors

Genotype: Rb1^tm1Tyj/Rb1⁺
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

endocrine/exocrine gland phenotype

increased pituitary gland tumor incidence
- in 9 of 10 mice; 5 of 5 with intermediate lobe origins

increased thyroid tumor incidence
- in 8 of 10 mice

mortality/aging

premature death
- median survival is 47 weeks

neoplasm

increased thyroid tumor incidence
- in 8 of 10 mice

increased pituitary gland tumor incidence
- in 9 of 10 mice; 5 of 5 with intermediate lobe origins

nervous system phenotype

increased pituitary gland tumor incidence
- in 9 of 10 mice; 5 of 5 with intermediate lobe origins

Genotype: Rb1^tm1Tyj/Rb1^tm1Tyj
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

cellular phenotype

abnormal cell differentiation
- transfection with a vector expressing Myhc partially rescues myocyte differentiation
- mouse embryonic fibroblasts transfected with a vector expressing Myod1 (MyoD) fail to differentiate into myocytes unlike similarly treated wild-type cells

mortality/aging

embryonic lethality, complete penetrance

Genotype: Rb1^tm1Tyj/Rb1⁺
involves: 129S2/SvPas

endocrine/exocrine gland phenotype

increased pituitary gland tumor incidence
- mice develop pituitary gland tumors with a mean survival of 400 days

mortality/aging

postnatal lethality, incomplete penetrance
- mice develop pituitary gland tumors with a mean survival of 400 days

neoplasm

increased pituitary gland tumor incidence
- mice develop pituitary gland tumors with a mean survival of 400 days

nervous system phenotype

increased pituitary gland tumor incidence
- mice develop pituitary gland tumors with a mean survival of 400 days

References

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):295-300PubMed: 1406933 MGI: J:2511

Additional References

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):6178-88PubMed: 8947040 MGI: 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):441-56PubMed: 8896600 MGI: J:36067

Additional - Rb1^tm1Tyj related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Rb1
- Genotyping resources and troubleshooting
Breeding Considerations

Mice homozygous for this targeted mutation die in utero. When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to FVB/NJ inbred mice (Stock No. 001800). The expected coat color from breeding is albino.
- Additional Breeding and Husbandry Support
Appearance
- albino, retinal degeneration
  Related Genotype: Tyr^c/Tyr^c Pde6b^rd1/Pde6b^rd1
Citation
When using the Rb^x3t mouse strain in a publication, please cite the originating article(s) and include JAX stock #002900 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Rb1<tm1Tyj>

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.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Rbx3t

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Additional Information

Selected References

Rb1tm1Tyj

Allele Symbol: Rb1tm1Tyj

Disease Terms

Research Areas By Phenotype

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

Genotype: Rb1tm1Tyj related

Mammalian Phenotype Terms by Genotype

Genotype: Rb1tm1Tyj/Rb1tm1Tyjinvolves: 129S2/SvPas * C57BL/6

behavior/neurological phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

integument phenotype

liver/biliary system phenotype

cardiovascular system phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

skeleton phenotype

cellular phenotype

Genotype: Rb1tm1Tyj/Rb1tm1Tyjinvolves: 129S2/SvPas

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

integument phenotype

liver/biliary system phenotype

mortality/aging

nervous system phenotype

vision/eye phenotype

cellular phenotype

embryo phenotype

Genotype: Rb1tm1Tyj/Rb1+involves: 129S2/SvPas * C57BL/6J

nervous system phenotype

respiratory system phenotype

endocrine/exocrine gland phenotype

mortality/aging

neoplasm

Genotype: Rb1tm1Tyj/Rb1+involves: 129S2/SvPas * C57BL/6

endocrine/exocrine gland phenotype

nervous system phenotype

growth/size/body region phenotype

mammalian phenotype

mortality/aging

neoplasm

Genotype: Rb1tm1Tyj/Rb1+involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

endocrine/exocrine gland phenotype

mortality/aging

neoplasm

nervous system phenotype

Genotype: Rb1tm1Tyj/Rb1tm1Tyjinvolves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

cellular phenotype

mortality/aging

Genotype: Rb1tm1Tyj/Rb1+involves: 129S2/SvPas

endocrine/exocrine gland phenotype

mortality/aging

neoplasm

nervous system phenotype

References

Additional References

Additional - Rb1tm1Tyj related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Also Known As:Rb^x3t

Rb1^tm1Tyj

Allele Symbol: Rb1^tm1Tyj

Genotype: Rb1^tm1Tyj related

Genotype: Rb1^tm1Tyj/Rb1^tm1Tyj
involves: 129S2/SvPas * C57BL/6

Genotype: Rb1^tm1Tyj/Rb1^tm1Tyj
involves: 129S2/SvPas

Genotype: Rb1^tm1Tyj/Rb1⁺
involves: 129S2/SvPas * C57BL/6J

Genotype: Rb1^tm1Tyj/Rb1⁺
involves: 129S2/SvPas * C57BL/6

Genotype: Rb1^tm1Tyj/Rb1⁺
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

Genotype: Rb1^tm1Tyj/Rb1^tm1Tyj
involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

Genotype: Rb1^tm1Tyj/Rb1⁺
involves: 129S2/SvPas

Additional - Rb1^tm1Tyj related