Overview

These OVE#2396B mice harbor a mutation created by random insertion of the Tyro-sd-IRES-loxP-FUGW lentiviral transgene (LV2187). The donating investigator reports the phenotype of homozygous mice as: males are sterile with small testes.

Donating Investigator

Paul A Overbeek, Baylor College of Medicine

Genetic overview

Genetic Background	Generation

Hsp90aa1^{Tg(Tyr)2396BOve}

Allele Type
Transgenic (Inserted expressed sequence)

View Genetics

Research Applications

Reproductive Biology Research

View All Research Applications

Details

Detailed Description

These OVE#2396B mice harbor a mutation created by random insertion of the Tyro-sd-IRES-loxP-FUGW lentiviral transgene (LV2187). Using inverse PCR analysis, the transgene integration site was identified in exon 9 of the heat shock protein 90, alpha, class A member 1 gene (Hsp90aa1) on chromosome 12 (specifically at the 3'-111,930,859(+) bp position). The donating investigator reports the phenotype of homozygous mice as: males are sterile with small testes.

Development

A lentiviral transgenic approach was used to generate these mice. The Tyro-sd-IRES-loxP-FUGW lentiviral transgene (LV2187) was designed with a mouse tyrosinase minigene (Tyro) followed by a splice-donor::IRES::loxP sequence in the FUGW self-inactivating HIV-based lentiviral vector backbone. The Tyro-sd-IRES-loxP replaced the ubiquitin-c promoter, EGFP, and WPRE sequences originally found in the FUGW lentiviral vector. The Tyro minigene is composed of the mouse Tyr enhancer region (620 bp), promoter region (500 bp), and 1.7 kbp cDNA sequence (including the stop codon); all in antisense orientation relative to the FUGW backbone. The Tyro minigene is followed by an artificial splice donor sequence, an internal ribosome entry site (IRES), and a loxP site in this construct. This packaged lentiviral construct was injected subzonally (under the zona pellucida) into 1-8 cell stage FVB/N mouse embryos. Because of the random and multiple lentiviral integration sites of a transgene containing tyrosinase, founder mice (F0) may be identified by mosaic pigmentation. Founder mice from line OVE#2396B were bred with FVB/N mice, and pigmented offspring (F1) were bred to FVB/N mice. The resulting offspring (F2) with identical coat colors (light grey) were subsequently inbred. Using inverse PCR analysis, the transgene integration site was identified in exon 9 of the heat shock protein 90, alpha, class A member 1 gene (Hsp90aa1) on chromosome 12 (specifically at the 3'-111,930,859(+) bp position). Transgenic males were sent to The Jackson Laboratory Repository (MMRRC-JAX). Upon arrival, these mice were bred to FVB/NJ inbred mice for at least one generation to establish the live colony.

Expression Data

Expressed Gene	Tyr, tyrosinase, mouse, laboratory
Site of Expression

Control Suggestions

Wild-type from the colony
001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Genetics

Hsp90aa1^{Tg(Tyr)2396BOve}

Allele Symbol: Hsp90aa1^{Tg(Tyr)2396BOve}

Allele Name	transgene lentiviral insertion 2396B, Paul A Overbeek
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	OVE#2396B; OVE2396B
Gene Symbol and Name	Hsp90aa1, heat shock protein 90, alpha (cytosolic), class A member 1
Gene Synonym(s)
Promoter	Tyr, tyrosinase, mouse, laboratory
Expressed Gene	Tyr, tyrosinase, mouse, laboratory
Strain of Origin	FVB/N
Chromosome	12
Molecular Note	The Tyro-IRES-sd-loxP-FUGW lentiviral transgene (LV2187) was designed with a mouse tyrosinase minigene (Tyro) followed by an IRES::3xATG::splice-donor::loxP sequence in the FUGW self-inactivating HIV-based lentiviral vector backbone. The Tyro-IRES-sd-loxP replaced the ubiquitin-c promoter, EGFP, and WPRE sequences originally found in the FUGW lentiviral vector. The Tyro minigene is composed of the mouse Tyr enhancer region (623 bp), promoter region (657 bp), and 1566 bp cDNA sequence (including the stop codon); all in antisense orientation relative to the FUGW backbone. The Tyro minigene is followed by an internal ribosome entry site (IRES) ending with ATGs in all three reading frames (3xATG), an artificial splice donor sequence, and a loxP site in this construct. In line 2396B, the lentiviral transgene inserted into exon 9 (NCBI37/mm9; 3'-111,930,859(+)).
Mutations Made By	Paul Overbeek, Baylor College of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Reproductive Biology Research
- Fertility Defects
  - males only

Mammalian Phenotype Terms by Genotype

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

Genotype: Hsp90aa1^{Tg(Tyr)2396BOve}/Hsp90aa1^{Tg(Tyr)2396BOve}
involves: C57BL/6 * FVB/N * FVB/NJ

cellular phenotype

abnormal photoreceptor connecting cilium morphology
- the connecting cilium is misplaced and less organized

increased retinal apoptosis
- photoreceptor apoptosis is seen in the 6-week old retina but not at 3 weeks of age

vision/eye phenotype

abnormal electroretinogram waveform feature
- ERG amplitudes of 3-week old mice are decreased and no ERG amplitude in response to light stimulation is seen at 20 weeks of age

abnormal photoreceptor connecting cilium morphology
- the connecting cilium is misplaced and less organized

abnormal photoreceptor outer segment disc membrane morphology
- outer segment membrane discs are twisted and coiled

abnormal photoreceptor outer segment morphology
- outer segments are swollen and deformed

abnormal retinal photoreceptor morphology
- Golgi apparatus is misplaced or broken/disintegrated in photoreceptors and not confined in the inner segment region and is distributed in a larger cytoplasmic area already at 3 weeks of age
- photoreceptors show aberrant intersegmental vesicle transportation

blindness
- mice are essentially blind by 20 weeks of age

decreased a wave amplitude
- a-wave amplitude of rod-ERG and max-ERG (combined functions of both rod and cone cells) are decreased at 3 and 20 weeks of age

decreased b wave amplitude
- b-wave amplitude of rod-ERG and max-ERG are decreased at 3 and 20 weeks of age

increased retinal apoptosis
- photoreceptor apoptosis is seen in the 6-week old retina but not at 3 weeks of age

photoreceptor inner segment degeneration
- inner segments are deteriorated with rough membrane surface and deformed shapes

retinal degeneration

retinal photoreceptor degeneration
- loss of photoreceptors is detected at 6 weeks of age and massive loss is seen by 15 weeks of age

thin retinal outer nuclear layer
- the outer nuclear layer is thinner in 6-week old mice

nervous system phenotype

abnormal photoreceptor connecting cilium morphology
- the connecting cilium is misplaced and less organized

abnormal photoreceptor outer segment disc membrane morphology
- outer segment membrane discs are twisted and coiled

abnormal photoreceptor outer segment morphology
- outer segments are swollen and deformed

abnormal retinal photoreceptor morphology
- Golgi apparatus is misplaced or broken/disintegrated in photoreceptors and not confined in the inner segment region and is distributed in a larger cytoplasmic area already at 3 weeks of age
- photoreceptors show aberrant intersegmental vesicle transportation

photoreceptor inner segment degeneration
- inner segments are deteriorated with rough membrane surface and deformed shapes

retinal photoreceptor degeneration
- loss of photoreceptors is detected at 6 weeks of age and massive loss is seen by 15 weeks of age

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

Genotype: Hsp90aa1^{Tg(Tyr)2396BOve}/Hsp90aa1^{Tg(Tyr)2396BOve}
FVB/N-Hsp90aa1

endocrine/exocrine gland phenotype

small testis

reproductive system phenotype

male infertility

small testis

References

Additional - Hsp90aa1^{Tg(Tyr)2396BOve} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Hsp90aa1-3'
- Separated PCR:Hsp90aa1-5'
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together, bred with wildtype siblings, or bred with FVB/N inbred mice.
- Additional Breeding and Husbandry Support
Citation
When using the FVB/N-Hsp90aa1^{Tg(Tyr)2396BOve}/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36273 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.

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Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Hsp90aa1Tg(Tyr)2396BOve

Allele Symbol: Hsp90aa1Tg(Tyr)2396BOve

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Hsp90aa1Tg(Tyr)2396BOve/Hsp90aa1Tg(Tyr)2396BOveinvolves: C57BL/6 * FVB/N * FVB/NJ

cellular phenotype

vision/eye phenotype

nervous system phenotype

Genotype: Hsp90aa1Tg(Tyr)2396BOve/Hsp90aa1Tg(Tyr)2396BOveFVB/N-Hsp90aa1

endocrine/exocrine gland phenotype

reproductive system phenotype

References

Additional - Hsp90aa1Tg(Tyr)2396BOve related

Genotyping Protocols

Breeding Considerations

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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Hsp90aa1^{Tg(Tyr)2396BOve}

Allele Symbol: Hsp90aa1^{Tg(Tyr)2396BOve}

Genotype: Hsp90aa1^{Tg(Tyr)2396BOve}/Hsp90aa1^{Tg(Tyr)2396BOve}
involves: C57BL/6 * FVB/N * FVB/NJ

Genotype: Hsp90aa1^{Tg(Tyr)2396BOve}/Hsp90aa1^{Tg(Tyr)2396BOve}
FVB/N-Hsp90aa1

Additional - Hsp90aa1^{Tg(Tyr)2396BOve} related