Overview

Disruption of Spo11 (SPO11 meiotic protein covalently bound to DSB homolog (S. cerevisiae)) leads to severe gonadal abnormalities in both males and females due to defective meiosis.

Donating Investigator

Maria Jasin, Memorial Sloan-Kettering Cancer Center

Scott Keeney, Memorial Sloan-Kettering Cancer Center

Genetic overview

Genetic Background	Generation

Spo11^tm1Mjn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Spo11	SPO11 meiotic protein covalently bound to DSB

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Research Applications

Reproductive Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Disruption of Spo11 (SPO11 meiotic protein covalently bound to DSB homolog (S. cerevisiae)) leads to severe gonadal abnormalities in both males and females due to defective meiosis.

These mice carry a targeted deletion of exons 4-6, removing a putative catalytic tyrosine encoded in exon 5. Northern blot analysis indicates that the null allele does not express transcripts.

Gonads from homozygous adult males are significantly reduced in weight. Spermatocytes undergo apoptotic death during early prophase. Oocytes from homozygous females progress to the diplotene/dictyate stage in nearly normal numbers, but most die soon after birth. Homozygotes also demonstrate defects in meiocyte homologous chromosomes and are unable to initiate meiotic recombination. Axial elements appear to be normal, but homologous synapsis is impaired.

Heterozygotes are fully fertile, but homozygous males and females are not. Homozygotes are born at predicted Mendelian ratios, indicating their viability is not affected.

Development

A targeting vector containing a neomycin resistance cassette was used to replace exons 4 to 6. The construct was electroporated into 129X1/SvJ-derived embryonic stem (ES) cells (Genome Systems). Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6J for 29 generations by the donating lab.

Control Suggestions

+/+ from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Baudat F; Manova K; Yuen JP; Jasin M; Keeney S. 2000. Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking spo11 Mol Cell 6(5):989-98PubMed: 11106739 MGI: J:65880

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Genetics

Spo11^tm1Mjn

Allele Symbol: Spo11^tm1Mjn

Allele Name	targeted mutation 1, Maria Jasin
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Maria Jasin; Spo11^tm1Mjn
Gene Symbol and Name	Spo11, SPO11 meiotic protein covalently bound to DSB
Gene Synonym(s)	CT35; SPATA43; AI449549; expressed sequence AI449549; TOPVIA; Spo11b; Spo11a
Strain of Origin	129X1/SvJ
Chromosome	2
Molecular Note	Exons 4-6 of this gene were replaced with a neomycin resistance cassette via homologous recombination thus deleting the putative catalytic tyrosine in exon 5. Northern blot assay failed to detect gene transcripts in testes of homozygous mutant males.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Reproductive Biology Research
- Developmental Defects Affecting Gonads
- Fertility Defects
- Meiotic Nondisjunction Studies

Mammalian Phenotype Terms by Genotype

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

Genotype: Spo11^tm1Mjn/Spo11^tm1Mjn
involves: 129X1/SvJ * C57BL/6

cellular phenotype

abnormal spermatid morphology
- absent

azoospermia
- absence of epididymal sperm

decreased oocyte number
- at 8 weeks of age oocyte depletion is more pronounced
- at P4 and P8 only 10% - 20% of the normal number of c-kit positive oocytes are seen
- normal numbers of oogonia are present at birth but oocyte numbers decline rapidly after birth

mammalian phenotype

immune system phenotype
- Normal - despite expression patterns and the known role in double strand breaks in meiosis, no abnormalities in somatic hypermutation or class switch recombination are detected

reproductive system phenotype

abnormal female meiosis
- Dcm1/Rad51 foci are nearly absent suggesting mice are unable to initiate meiotic recombination
- oocytes display defects in synapsis

abnormal male meiosis
- Dcm1/Rad51 foci are nearly absent suggesting mice are unable to initiate meiotic recombination
- few or no cells progress through meiosis
- spermatocyte nuclei with complete synapsis are not seen
- spermatocytes are seen with much longer axial elements and short synaptonemal complexes, with longer synaptonemal complexes but axial elements involved in synapsis with several partners, or without synaptonemal complexes

abnormal oogenesis
- at E15.5 most oocytes appear to be in the leptotene or early zygotene stage
- at E16.5 most oocytes still have an early zygotene morphology with a few reaching an abnormal zygotene like stage with long axial elements in synapsis but with partner exchanges
- at E17.5 most nuclei are either in an abnormal zygotene like stage or have appear to be fully synapsed but lack Scp1 expression

abnormal ovary morphology
- at 8 weeks of age ovarian dysgenesis is apparent

abnormal primordial ovarian follicle morphology
- at P13 the cortex of the ovary is nearly devoid of primordial follicles

abnormal spermatid morphology
- absent

abnormal spermatogenesis
- increase in the incidence of apoptotic cells in the tubules

arrest of spermatogenesis
- no spermatocytes with pachytene or later morphology are seen
- seminiferous tubules generally contain only spermatogonia and Sertoli cells or spermatogonia and Sertoli cells plus either early prophase spermatocytes or cells with highly condensed chromatin fragments

azoospermia
- absence of epididymal sperm

decreased mature ovarian follicle number
- at 10 weeks of age only a few intermediate stage follicles and a single preovulatory follicle are seen

decreased oocyte number
- at 8 weeks of age oocyte depletion is more pronounced
- at P4 and P8 only 10% - 20% of the normal number of c-kit positive oocytes are seen
- normal numbers of oogonia are present at birth but oocyte numbers decline rapidly after birth

decreased testis weight
- at 10 and 14 weeks of age testis weights are 20% - 50% of wild-type or heterozygous littermates

female infertility

impaired ovarian folliculogenesis
- at 10 weeks of age only a few intermediate stage follicles and a single preovulatory follicle are seen
- at P13, after the first cohort of oocytes is normally recruited to grow, the number of growing follicles is reduced 2 fold

male infertility

small ovary
- slightly smaller compared to wild-type mice

small seminiferous tubules

endocrine/exocrine gland phenotype

abnormal ovary morphology
- at 8 weeks of age ovarian dysgenesis is apparent

abnormal primordial ovarian follicle morphology
- at P13 the cortex of the ovary is nearly devoid of primordial follicles

decreased mature ovarian follicle number
- at 10 weeks of age only a few intermediate stage follicles and a single preovulatory follicle are seen

decreased testis weight
- at 10 and 14 weeks of age testis weights are 20% - 50% of wild-type or heterozygous littermates

impaired ovarian folliculogenesis
- at 10 weeks of age only a few intermediate stage follicles and a single preovulatory follicle are seen
- at P13, after the first cohort of oocytes is normally recruited to grow, the number of growing follicles is reduced 2 fold

small ovary
- slightly smaller compared to wild-type mice

small seminiferous tubules

Genotype: Spo11^tm1Mjn/Spo11^tm1Mjn
involves: 129X1/SvJ * C57BL/6JOlaHsd

cellular phenotype

decreased oocyte number
- very few oocytes survive until 6 weeks unlike in wild-type mice

oocyte degeneration
- at P1, oocyte apoptosis rates are higher than in wild-type cells

reproductive system phenotype

abnormal female meiosis
- pseudo-sex-body-like formation is impaired compared to in wild-type cells

arrest of spermatogenesis
- spermatocytes are eliminated in stage-IV tubules unlike in wild-type mice

decreased oocyte number
- very few oocytes survive until 6 weeks unlike in wild-type mice

oocyte degeneration
- at P1, oocyte apoptosis rates are higher than in wild-type cells

Genotype: Spo11^tm1Mjn/Spo11^tm1Mjn
involves: 129X1/SvJ

cellular phenotype

decreased oocyte number
- much lower numbers at 6 weeks of age

endocrine/exocrine gland phenotype

decreased ovary weight

small ovary

reproductive system phenotype

abnormal female meiosis
- pseudo-sex body formation in oocytes is impaired

abnormal meiosis
- a subset of unsynapsed chromosome axes are surrounded by H2AFX rich chromatin domains forming pseudo-sex bodies

abnormal synaptonemal complex
- extensive non-homologous synaptonemal complex formation

decreased oocyte number
- much lower numbers at 6 weeks of age

decreased ovary weight

small ovary

Genotype: Spo11^tm1Mjn/Spo11^tm1Mjn
involves: 129X1/SvJ * C57BL/6J

cellular phenotype

abnormal double-strand DNA break repair
- double-strand break formation is abolished

homeostasis/metabolism phenotype

abnormal double-strand DNA break repair
- double-strand break formation is abolished

reproductive system phenotype

abnormal chromosomal synapsis
- spermatocytes exhibit homolog association and pairing at all tested chromosomal regions, although less than in wild-type spermatocytes

abnormal male meiosis
- spermatocytes exhibit homolog association and pairing at all tested chromosomal regions, although less than in wild-type spermatocytes
- spermatocytes form cohesion axes and axial elements but fail to undergo proper synapsis, arresting at the late leptotene or zygotene-like stage
- spermocytes exhibit neither early centromere-associations nor preferential initiation of synaptonemal complex formation from centromeres

arrest of male meiosis
- spermatocytes arrest at the late leptotene or zygotene-like stage

References

Baudat F; Manova K; Yuen JP; Jasin M; Keeney S. 2000. Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking spo11 Mol Cell 6(5):989-98PubMed: 11106739 MGI: J:65880

Additional - Spo11^tm1Mjn related

Technical Support

Contact Technical Support

Genotyping Protocols
- SEPARATED MELT: Spo11^tm1Mjn
- Separated PCR: Spo11^tm1Mjn
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes are viable but infertile.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129X1-Spo11^tm1Mjn/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019117 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

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Genotype

Price

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Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or Wildtype for Spo11<tm1Mjn>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Spo11tm1Mjn

Allele Symbol: Spo11tm1Mjn

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Spo11tm1Mjn/Spo11tm1Mjninvolves: 129X1/SvJ * C57BL/6

cellular phenotype

mammalian phenotype

reproductive system phenotype

endocrine/exocrine gland phenotype

Genotype: Spo11tm1Mjn/Spo11tm1Mjninvolves: 129X1/SvJ * C57BL/6JOlaHsd

cellular phenotype

reproductive system phenotype

Genotype: Spo11tm1Mjn/Spo11tm1Mjninvolves: 129X1/SvJ

cellular phenotype

endocrine/exocrine gland phenotype

reproductive system phenotype

Genotype: Spo11tm1Mjn/Spo11tm1Mjninvolves: 129X1/SvJ * C57BL/6J

cellular phenotype

homeostasis/metabolism phenotype

reproductive system phenotype

References

Additional - Spo11tm1Mjn related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

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

Spo11^tm1Mjn

Allele Symbol: Spo11^tm1Mjn

Genotype: Spo11^tm1Mjn/Spo11^tm1Mjn
involves: 129X1/SvJ * C57BL/6

Genotype: Spo11^tm1Mjn/Spo11^tm1Mjn
involves: 129X1/SvJ * C57BL/6JOlaHsd

Genotype: Spo11^tm1Mjn/Spo11^tm1Mjn
involves: 129X1/SvJ

Genotype: Spo11^tm1Mjn/Spo11^tm1Mjn
involves: 129X1/SvJ * C57BL/6J

Additional - Spo11^tm1Mjn related