Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Marvin Meistrich,   University of Texas M.D. Anderson Cancer

Description
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern or Western blot analysis. Homozygous female mice are fertile. Homozygous male mice are subfertile, producing small litters. Sperm retention in seminiferous tubules of mutant mice is due to increased sperm tail abnormalities. Transition protein 1 and precursor and partially processed protamine 2 levels are elevated in testis tissue. Electron microscopy analysis of mutant testis tissue reveals abnormal cylindrical focal chromatin condensation morphology in spermatids and incomplete chromatin condensation with lacunae and granularity in late stage spermatids and epididymal sperm. Increased uptake of DNA intercalating dyes by mutant sperm nuclei and susceptibility of mutant sperm DNA to acid denaturation is indicative of DNA strand breakage. This mutant mouse strain may be useful in studies of male infertility and/or subfertility.

Development
A targeting vector containing a neomycin resistance gene flanked by loxP sites and a herpes simplex virus thymidine kinase genes was used to disrupt the entire targeted gene. The construct was electroporated into 129S7/SvEvBrd-Hprt⁺ derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tnp2^tm1Mzh/Tnp2^tm1Mzh

        involves: 129S/SvEv * 129S7/SvEvBrd

• reproductive system phenotype
• asthenozoospermia (MGI Ref ID J:72107)
  • sperm retention was noted on seminiferous tubules
• decreased litter size (MGI Ref ID J:72107)
  • the litter size produced from matings involving homozygous males was almost half the size of controls
• teratozoospermia (MGI Ref ID J:72107)
  • bent midpieces, unraveled axonome and outer dense fibers; abnormal chromatin condensation in spermatids and sperm

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

Tnp2^tm1Mzh/Tnp2^tm1Mzh

        involves: 129S7/SvEvBrd * C57BL/6J

• normal phenotype
• no abnormal phenotype detected (MGI Ref ID J:72107)
  • although a trend toward reduced litter size and abnormal sperm morphology was noted, the differences from controls were not statistically significant

View Research Applications

Research Applications

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

Tnp2^tm1Mzh related

Reproductive Biology Research
Fertility Defects (males only)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tnp2tm1Mzh
Allele Name		targeted mutation 1, Ming Zhao
Allele Type		Targeted (knock-out)
Common Name(s)		Tnp2-;
Mutation Made By		Marvin Meistrich,   University of Texas M.D. Anderson Cancer
Strain of Origin		129S7/SvEvBrd-Hprt1+
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/SvEvBrd-Hprt1<+>
Gene Symbol and Name		Tnp2, transition protein 2
Chromosome		16
Gene Common Name(s)		MGC116783; MGC116785; TP2; Tp-2;
Molecular Note		The entire gene was replaced with a neo cassette flanked by loxP sites via homologous recombination. Northern and Western blot analysis verified the absence of gene expression in testes of homozygous mutant animals. [MGI Ref ID J:72107]

Genotyping

Genotyping Information

Genotyping Protocols

NEOTD (Generic Neo), STD PCR, vers. 1
Tnp2^tm1Mzh, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Zhao M; Shirley CR; Yu YE; Mohapatra B; Zhang Y; Unni E; Deng JM; Arango NA; Terry NH; Weil MM; Russell LD; Behringer RR; Meistrich ML. 2001. Targeted disruption of the transition protein 2 gene affects sperm chromatin structure and reduces fertility in mice. Mol Cell Biol 21(21):7243-55. [PubMed: 11585907]  [MGI Ref ID J:72107]

Additional References

Zhao M; Shirley CR; Hayashi S; Marcon L; Mohapatra B; Suganuma R; Behringer RR; Boissonneault G; Yanagimachi R; Meistrich ML. 2004. Transition nuclear proteins are required for normal chromatin condensation and functional sperm development. Genesis 38(4):200-13. [PubMed: 15083521]  [MGI Ref ID J:89779]

Tnp2^tm1Mzh related

Shirley CR; Hayashi S; Mounsey S; Yanagimachi R; Meistrich ML. 2004. Abnormalities and reduced reproductive potential of sperm from Tnp1- and Tnp2-null double mutant mice. Biol Reprod 71(4):1220-9. [PubMed: 15189834]  [MGI Ref ID J:93181]

Suganuma R; Yanagimachi R; Meistrich ML. 2005. Decline in fertility of mouse sperm with abnormal chromatin during epididymal passage as revealed by ICSI. Hum Reprod 20(11):3101-8. [PubMed: 16037114]  [MGI Ref ID J:106637]

Zhao M; Shirley CR; Hayashi S; Marcon L; Mohapatra B; Suganuma R; Behringer RR; Boissonneault G; Yanagimachi R; Meistrich ML. 2004. Transition nuclear proteins are required for normal chromatin condensation and functional sperm development. Genesis 38(4):200-13. [PubMed: 15083521]  [MGI Ref ID J:89779]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The resulting male chimeric animals were crossed to 129S6/SvEvTac females. This strain is maintained as heterozygous males and homozygous females.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. 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. This strain is included in the Induced Mutant Resource Colony collection.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.