Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Heterozygote         (Female x Male)   22-DEC-09 Species laboratory mouse Generation F?+F3 (03-SEP-10) Generation Definitions   Donating Investigator Martin Matzuk,   Baylor College of Medicine

Description
Female mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous males are infertile due to severe abnormal spermatozoa morphology and diminished sperm motility. Heterozygous males exhibit terato-asthenozoospermia (increase in the percentage of abnormal sperm) and globozoospermia, but are fertile with normal fecundity.

Electron microscopic examination of sperm reveals ultrastructural abnormalties. No gene product (mRNA or protein) is detected by Northern or Western blot analysis or testicular tissue and sperm. This mutant mouse strain may be useful in studies of acrosomal biogenesis and spermiogenesis.

Development
A targeting vector containing a PgkHPRT cassette was used to disrupt exons 1 and 2, which encode the signal peptide region. The construct was electroporated into 129S7/SvEvBrd-Hprt1^b-m2 derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting male chimeric animals were crossed to C57BL/6J female mice. The mice were maintained on a B6;129S7 background before arriving at The Jackson Laboratory.

Control Information

	Control
	101043 B6129SF1/J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Zpbp^tm1Zuk/Zpbp⁺

        involves: 129S7/SvEvBrd * C57BL/6J

• reproductive system phenotype
• teratozoospermia
  • increase in the percentage of abnormal sperm   (MGI Ref ID J:126661)
  • however, fecundity is similar to wild-type males   (MGI Ref ID J:126661)

Zpbp^tm1Zuk/Zpbp^tm1Zuk

        involves: 129S7/SvEvBrd * C57BL/6J

• reproductive system phenotype
• *normal* reproductive system phenotype
  • total testis weight is similar to wild-type and heterozygous littermates   (MGI Ref ID J:126661)
• • abnormal Sertoli cell morphology
    • abnormal vesicles made of acrosome fragments coated with junctional structures are present in the cytoplasm   (MGI Ref ID J:126661)
  • abnormal spermatogenesis
    • profound fragmentation and degradation of the acrosome in spermatids   (MGI Ref ID J:126661)
  • • abnormal spermatid morphology
      • dilated acrosome, detached of eccentric acrosomal granules, and occasional nuclear indentation by the dilated acrosome are seen as early as in step 6 to 8 spermatids   (MGI Ref ID J:126661)
    • teratozoospermia
      • additional abnormalities including misshapen nuclei, detached flagella, and disorganized mitochondria within excessive cytoplasmic droplets are seen   (MGI Ref ID J:126661)
    • • abnormal acrosome morphology
        • only abnormally shaped acrosome fragments are seen in ~20% of sperm   (MGI Ref ID J:126661)
      • • absent acrosome
          • the acrosome is absent in over 80% of sperm   (MGI Ref ID J:126661)
        • globozoospermia
          • most caudal epididymal sperm have a round-head with the tail coiled around the nucleus   (MGI Ref ID J:126661)
      • abnormal sperm flagellum morphology
        • disorganized mitochondria within excessive cytoplasmic droplets are seen   (MGI Ref ID J:126661)
      • • coiled sperm flagellum
          • the proportion of sperm with coiled flagella increases from the proximal caput epididymis to the caudal epididymis   (MGI Ref ID J:126661)
        • detached sperm flagellum   (MGI Ref ID J:126661)
      • abnormal sperm nucleus morphology
        • misshapen nuclei are observed   (MGI Ref ID J:126661)
  • asthenozoospermia
    • only about 10% of sperm are motile compared to 68% motility in controls   (MGI Ref ID J:126661)
  • male infertility
    • secondary to globozoospermia   (MGI Ref ID J:126661)
    • despite normal sperm counts   (MGI Ref ID J:126661)
    • however, female fertility is normal   (MGI Ref ID J:126661)
• endocrine/exocrine gland phenotype
• abnormal Sertoli cell morphology
  • abnormal vesicles made of acrosome fragments coated with junctional structures are present in the cytoplasm   (MGI Ref ID J:126661)

View Research Applications

Research Applications

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

Reproductive Biology Research
Fertility Defects
      males only

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Zpbptm1Zuk
Allele Name		targeted mutation 1, Martin M Matzuk
Allele Type		Targeted (knock-out)
Common Name(s)		Zpbp1-; Zpbp1tm1Zuk;
Mutation Made By		Yi-Nan Lin,   IBMS, Academia Sinica
Strain of Origin		129S7/SvEvBrd-Hprt
ES Cell Line Name		AB2.2
ES Cell Line Strain		129S7/SvEvBrd-Hprt
Gene Symbol and Name		Zpbp, zona pellucida binding protein
Chromosome		11
Gene Common Name(s)		4930486K01Rik; RIKEN cDNA 4930486K01 gene; Sp38; ZPBP1;
Molecular Note		Exons 1 and 2 were replaced with a PgkHPRT cassette via homologous recombination. This resulted in deletion of the signal peptide encoding region. Northern and Western blot analysis confirmed the absence of RNA transcript and protein in the testes. [MGI Ref ID J:126661]

Genotyping

Genotyping Information

Genotyping Protocols

Zpbp^tm1Zuk, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lin YN; Roy A; Yan W; Burns KH; Matzuk MM. 2007. Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Mol Cell Biol 27(19):6794-805. [PubMed: 17664285]  [MGI Ref ID J:126661]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygous females and heterozygous males. Homozygous females are fertile, homozygous males are infertile due to severe abnormal spermatozoa morphology and diminished sperm motility.
Mating System	Homozygote x Heterozygote         (Female x Male)   22-DEC-09
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

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

Control Information

	Control
	101043 B6129SF1/J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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