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   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 (protein) is detected in testicular homogenates. Levels of transition nuclear protein 2 and protamine 2 precursor are elevated. Homozygous female mice are fertile. Homozygous male mice are subfertile, approximately 60% are infertile, and display diminished sperm motility, sperm tail abnormalities and sperm chromatin abnormalities. Electron microscopy analysis of spermatids reveals both abnormal large rod-like chromatin condensation units as well as normal fine fibrillar chromatin morphology. This mutant mouse strain may be useful in studies of male infertility and/or subfertility.

Development
A targeting vector containing neomycin resistance and thymidine kinase genes was used to replace 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/6 blastocysts. The resulting male chimeric animals were backcrossed to 129S6/SvEvTac female mice.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Tnp1^tm1Mlm/Tnp1^tm1Mlm

        involves: 129S7/SvEvBrd * C57BL/6J

• reproductive system phenotype
• *normal* reproductive system phenotype
  • homozygotes exhibit no differences in testis and seminal vesicle weights and sperm counts relative to wild-type and heterozygous controls   (MGI Ref ID J:61941)
• • abnormal sperm nucleus morphology
    • homozygotes display a significantly higher frequency of epididymal sperm heads in which the nuclear apex is bent or blunted   (MGI Ref ID J:61941)
    • large rod-like chromatin condensation units are observed in nuclei of mutant step 13 spermatids, unlike the fine chromatin fibrils observed in wild type; after step 14, all of the chromatin becomes condensed and darkly stained with hematoxylin   (MGI Ref ID J:61941)
  • abnormal spermatid morphology
    • EM revealed large rod-like chromatin condensation units in the nuclei of mutant step 13 spermatids, in contrast to the fine chromatin fibrils observed in wild type   (MGI Ref ID J:61941)
  • abnormal spermiogenesis
    • in steps 12 and 13, mutant spermatid nuclei exhibit increased levels of transition protein 2 (TNP2), accounting for 91% of the basic nuclear protein, as well as increased levels of protamine 2 precursor pP2 (2%-11% vs 0% in controls); in contrast, histone displacement occurs normally   (MGI Ref ID J:61941)
    • in steps 14-16 spermatids, pP2 is 21% of the total nuclear protein relative to only 10% and 5% in heterozygous and wild-type males, respectively, and the ratio of pP2 to pP2/11 is increased, suggesting abnormal P2 processing   (MGI Ref ID J:61941)
    • although most of the precursor is processed to mature P2, high levels of incompletely processed forms pesist in epididymal spermatozoa   (MGI Ref ID J:61941)
  • asthenozoospermia
    • only 23% of mutant sperm exhibit any motility   (MGI Ref ID J:61941)
    • most of these sperm fail to show forward progression   (MGI Ref ID J:61941)
  • coiled sperm flagellum
    • mutant sperm with tails coiled around the heads are observed   (MGI Ref ID J:61941)
    • however, most cauda epididymal sperm appear relatively normal   (MGI Ref ID J:61941)
  • decreased litter size
    • whereas fertile B6 x 129 F2 male homozygotes (16 weeks of age) exhibit normal litter sizes relative to wild-type controls, those on an inbred 129 background (9 weeks of age) display a 70% reduction in litter size relative to wild-type and heterozygous controls   (MGI Ref ID J:61941)
  • male infertility
    • 70% of male homozygotes are infertile on a hybrid genetic background (B6 x 129 F2) versus 60% on an inbred 129 background   (MGI Ref ID J:61941)
  • reduced male fertility
    • fertile homozygotes on both the B6 × 129 F2 and 129 backgrounds produce a reduced number of litters/pair relative to wild-type controls   (MGI Ref ID J:61941)

View Research Applications

Research Applications

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

Tnp1^tm1Mlm related

Reproductive Biology Research
Fertility Defects
      males only

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tnp1tm1Mlm
Allele Name		targeted mutation 1, Marvin L Meistrich
Allele Type		Targeted (knock-out)
Common Name(s)		Tnp1-; Tnp1-null;
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		Tnp1, transition protein 1
Chromosome		1
Gene Common Name(s)		Stp-1; TP1; Tp-1; spermatid transition protein 1;
Molecular Note		The entire gene was replaced with a neomycin cassette, which was inserted in an antisense orientation. Tnp1 protein was not detectable in extracts of testicular homogenates from homozygous mutant mice. [MGI Ref ID J:61941]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Yu YE; Zhang Y; Unni E; Shirley CR; Deng JM; Russell LD; Weil MM; Behringer RR; Meistrich ML. 2000. Abnormal spermatogenesis and reduced fertility in transition nuclear protein 1-deficient mice. Proc Natl Acad Sci U S A 97(9):4683-8. [PubMed: 10781074]  [MGI Ref ID J:61941]

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]

Tnp1^tm1Mlm related

Liebe B; Petukhova G; Barchi M; Bellani M; Braselmann H; Nakano T; Pandita TK; Jasin M; Fornace A; Meistrich ML; Baarends WM; Schimenti J; de Lange T; Keeney S; Camerini-Otero RD; Scherthan H. 2006. Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages. Exp Cell Res 312(19):3768-81. [PubMed: 17010969]  [MGI Ref ID J:147391]

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]

Zhao M; Shirley CR; Mounsey S; Meistrich ML. 2004. Nucleoprotein transitions during spermiogenesis in mice with transition nuclear protein Tnp1 and Tnp2 mutations. Biol Reprod 71(3):1016-25. [PubMed: 15163613]  [MGI Ref ID J:107120]

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	This strain originated on a 129S7 background, has been backcrossed to the 129S6/SvEvTac background and is maintained as heterozygous males and homozygous females.

Purchasing information

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• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

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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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