Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+F1p (15-JAN-06) Generation Definitions   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 provided by MGI

      assigned by genotype

Tnp2^tm1Mzh/Tnp2^tm1Mzh

        involves: 129S/SvEv * 129S7/SvEvBrd

• reproductive system phenotype
• asthenozoospermia
  • sperm retention was noted on seminiferous tubules   (MGI Ref ID J:72107)
• decreased litter size
  • the litter size produced from matings involving homozygous males was almost half the size of controls   (MGI Ref ID J:72107)
• teratozoospermia
  • significant increase in sperm flagellum, but not head, abnormalities relative to wild-type or heterozygous mice   (MGI Ref ID J:72107)
• • abnormal sperm axoneme morphology
    • significant increase in the number of sperm with unraveled axoneme and/or outer dense fibers (14%) relative to wild-type controls (2%)   (MGI Ref ID J:72107)
  • abnormal sperm midpiece morphology
    • significant increase in number of sperm with bent midpieces (26%) relative to wild-type controls (5%)   (MGI Ref ID J:72107)
  • abnormal sperm nucleus morphology
    • aberrant focal condensations of chromatin in step 11 to 13 spermatids   (MGI Ref ID J:72107)
    • progressive chromatin condensation in later spermatids, but incomplete condensation in epididymal sperm   (MGI Ref ID J:72107)
    • sperm chromatin is more accessible to intercalating dyes and more susceptible to acid denaturation, suggesting DNA strand breaks   (MGI Ref ID J:72107)

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
  • although a trend toward reduced litter size and abnormal sperm morphology was noted, the differences from controls were not statistically significant   (MGI Ref ID J:72107)

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 provided by MGI

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-Hprt<+>
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/SvEvBrd-Hprt<+>
Gene Symbol and Name		Tnp2, transition protein 2
Chromosome		16
Gene Common Name(s)		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

Tnp2^tm1Mzh, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

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 Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

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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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