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Transgenic ZP2 Mouse Model Produces Eggs That Bind to Human Sperm Protein

Posted Jun 05 2012 8:00pm

Description of Invention:
Fertilizing sperm bind to an extracellular coat surrounding mammalian eggs called zona pellucida. Depending on the species, the zona pellucida is composed of ZP1, ZP2, ZP3, and/or ZP4 proteins. Recent studies show that sperm successfully adhere to the zona pellucida surface when ZP2 is intact. In contrast, when ZP2 has been proteolytically cleaved, sperm binding is disrupted.

To further study the effect of ZP2 cleavage in sperm-egg recognition, researchers at NIDDK have developed a transgenic mouse expressing human ZP2. Prior attempts using ZP2 knockout mice were unsuccessful because the produced eggs were not fertile in vivo. Transgenic ZP2 mice produced humanized zonae pellucida, and produced fertile eggs to which human sperm successfully and specifically bound. This mouse model contradicts previous notions that production of human transgenic ZP2 would adversely change the specificity of sperm binding.

  • Transgenic eggs can be used in diagnostic functional assays to assess human sperm viability for reproductive technologies.
  • Diagnostic assay can be extended to determine presence of male infertility in a variety of mammals, including pets, farm livestock, and zoological mammals.

  • This ZP2 mice model produces eggs containing transgenic mammalian zona pellucida, which can successfully and specifically be fertilized with the corresponding mammalian sperm.
  • Use in human infertility studies spares the use of a human egg for binding studies.

Development Status:
  • Prototype
  • Early-stage
  • In vitro data available
  • In vivo data available (animal)

Jurrien Dean (NIDDK)
Tracy L Rankin (NIDDK)
Eric JM Lee (NICHD)
Scott Turner (NIDDK)

Patent Status:
HHS, Reference No. E-288-2011/0

Research Tool — Patent protection is not being pursued for this technology.

Related Technologies:
EIR, Reference No. E-162-2011/0

Research Tool — Patent protection is not being pursued for this technology.

Relevant Publication:
  1. Rankin TL, et al. [ PMID 12852850 ]
  2. Gahlay G, et al. [ PMID 20616279 ]

For Licensing Information Please Contact:
Lauren Nguyen-Antczak Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-496-7057
Fax: 301-402-0220

Ref No: 2449

Updated: 06/2012

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