Overview

Mice expressing the IRBP-Tag allele develop hereditary retinoblastomas, pineal tumors, narrowed ocular fissures and exophthalmia. These mice may be useful for studying heritable ocular tumors of photoreceptor cell origin and pineal tumors associated with retinoblastoma.

Donating Investigator

Daniel M. Albert, University of Wisconsin

Genetic overview

Genetic Background	Generation

Tg(Rbp3-SV40)IT-2Jjw

Allele Type
Transgenic (Inserted expressed sequence)

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Research Applications

Mouse/Human Gene Homologs
Sensorineural Research
Developmental Biology Research
Research Tools

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Details

Detailed Description

Mice hemizygous for the IRBP-Tag allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Expression of Tag is regulated by a murine interstitial retinol binding protein (IRBP) promoter (rbp3), which leads to expression of Tag in photoreceptor cells of the developing retina before their terminal differentiation. This expression results in hereditary retinoblastomas and pineal tumors arising from photoreceptor cells and pinealocytes, which may share a common evolutionary ancestor with retinal cells. IRBP-Tag mice develop narrowed ocular fissures by 3 to 4 weeks of age, and exophthalmia by 8 weeks of age. The pineal gland is enlarged by 5 to 6 weeks of age, and is no longer intact by 8 to 10 weeks of age when the tumor covers and invades the cerebral and cerebellar hemispheres. These mice may be useful for studying heritable ocular tumors of photoreceptor cell origin and pineal tumors associated with retinoblastoma.

Development

The IRBP-Tag transgene contains the simian virus 40 (SV40) early region encoding both large T-antigen (Tag) and small t-antigen under the control of murine interstitial retinol binding protein (IRBP) promoter (rbp3). The construct was microinjected into fertilized oocytes obtained from matings of CB6F1/Hsd (BALB/cAnNHsd inbred female bred to C57BL/6NHsd inbred male), and offspring from founder line IT-2 were bred to CB6F1/Hsd nontransgenic mice to establish a colony. Upon arrival at The Jackson Laboratory, mice were bred to CB6F1/J hybrid mice for at least one generation to establish the colony.

Expression Data

Expressed Gene	SV40, E mu enhancer, SV40
Site of Expression

Control Suggestions

100007 CB6F1/J

Additional Information

Considerations for Choosing Controls

Selected References

Howes KA; Lasudry JG; Albert DM; Windle JJ. 1994. Photoreceptor cell tumors in transgenic mice. Invest Ophthalmol Vis Sci 35(2):342-51PubMed: 8112979 MGI: J:60231

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Genetics

Tg(Rbp3-SV40)IT-2Jjw

Allele Symbol: Tg(Rbp3-SV40)IT-2Jjw

Allele Name	transgene insertion IT-2, Jolene J Windle
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	IRBP-Tag
Gene Symbol and Name	Tg(Rbp3-SV40)IT-2Jjw, transgene insertion IT-2, Jolene J Windle
Gene Synonym(s)
Promoter	Rbp3, retinol binding protein 3, interstitial, mouse, laboratory
Expressed Gene	SV40, E mu enhancer, SV40
Strain of Origin	(BALB/cAnNHsd x C57BL/6NHsd)F2
Chromosome	UN
General Note	Transgenic animals develop retinal and pineal tumors by 10-12 weeks of age with 100% penetrance. Transgenic animals carrying the greatest transgene copy number (15-50) also displayed a 25%-30% decrease in body weight compared to non-transgenic animals.
Molecular Note	2.7 kb of the SV40 T antigen gene fused to 1.9 kb of mouse RBP3 promoter sequences was used as the transgene. Promoter sequences from -1783 to +101 were used to drive expression of the transgene in photoreceptor cells. Northern blot analysis confirmed transgene expression in the retina and pineal of transgenic animals.

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

retinoblastoma

Research Areas By Phenotype

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

Mouse/Human Gene Homologs
- retinal degeneration, slow
Sensorineural Research
- Eye Defects
Developmental Biology Research
- Eye Defects
Research Tools
- Sensorineural Research
  - retinal degeneration

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Tg(Rbp3-SV40)IT-2Jjw/?
involves: BALB/c * C57BL/6

nervous system phenotype

enlarged pineal gland
- pineal gland is replaced by tumor cells
- pineal gland is consistently enlarged by 5 to 6 weeks of age

increased pineal gland tumor incidence
- by 2 weeks of age the pineal gland is replaced by tumor cells that resemble a highly differentiated retinoblastoma in 2 week old mice
- by 8-10 weeks of age tumors cover and invade the cerebral and cerebellar hemispheres
- tumor cells form Homer Wright rosettes
- 25% of mice develop midbrain tumors
- cells are large and atypical with numerous abnormal mitotic figures

vision/eye phenotype

exophthalmos
- mice develop exophthalmia by 8 weeks of age

increased retinoblastoma incidence
- mice develop ocular tumors of photoreceptor cell origin
- beginning at 4 weeks of age, photoreceptor cells are replaced by hyperchromatic cells of small size with scanty cytoplasm
- by 10 weeks of age tumors invade the optic nerve, ciliary body, iris and vitreous

abnormal retina morphology
- beginning in the inner nuclear layer, neoplastic cells invade the bipolar layer of the retina by 6-8 weeks of age
- mice exhibit narrowing of the ocular fissures by 3 to 4 weeks of age

cataract
- 4 week old mice exhibit cataracts

endocrine/exocrine gland phenotype

increased pineal gland tumor incidence
- tumor cells form Homer Wright rosettes
- by 2 weeks of age the pineal gland is replaced by tumor cells that resemble a highly differentiated retinoblastoma in 2 week old mice
- by 8-10 weeks of age tumors cover and invade the cerebral and cerebellar hemispheres
- 25% of mice develop midbrain tumors
- cells are large and atypical with numerous abnormal mitotic figures

enlarged pineal gland
- pineal gland is consistently enlarged by 5 to 6 weeks of age
- pineal gland is replaced by tumor cells

neoplasm

increased pineal gland tumor incidence
- 25% of mice develop midbrain tumors
- cells are large and atypical with numerous abnormal mitotic figures
- tumor cells form Homer Wright rosettes
- by 2 weeks of age the pineal gland is replaced by tumor cells that resemble a highly differentiated retinoblastoma in 2 week old mice
- by 8-10 weeks of age tumors cover and invade the cerebral and cerebellar hemispheres

increased retinoblastoma incidence
- mice develop ocular tumors of photoreceptor cell origin
- beginning at 4 weeks of age, photoreceptor cells are replaced by hyperchromatic cells of small size with scanty cytoplasm
- by 10 weeks of age tumors invade the optic nerve, ciliary body, iris and vitreous

References

Howes KA; Lasudry JG; Albert DM; Windle JJ. 1994. Photoreceptor cell tumors in transgenic mice. Invest Ophthalmol Vis Sci 35(2):342-51PubMed: 8112979 MGI: J:60231

Additional - Tg(Rbp3-SV40)IT-2Jjw related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, hemizygous mice may be bred to CB6F1/J hybrid mice. The donating investigator reports always breeding hemizygous mice to CB6F1 mice.
- Additional Breeding and Husbandry Support
Mating System
- See "Breeding Considerations"
Citation
When using the CB6-Tg(Rbp3-SV40)IT-2Jjw/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32030 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

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

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(Rbp3-SV40)IT-2Jjw

Allele Symbol: Tg(Rbp3-SV40)IT-2Jjw

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Rbp3-SV40)IT-2Jjw/?involves: BALB/c * C57BL/6

nervous system phenotype

vision/eye phenotype

endocrine/exocrine gland phenotype

neoplasm

References

Additional - Tg(Rbp3-SV40)IT-2Jjw related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Genotype: Tg(Rbp3-SV40)IT-2Jjw/?
involves: BALB/c * C57BL/6