Zona pellucida binding protein 2 or Zpbp2 is a sulfated glycoprotein found in spermatid and spermatozoon and localized to the acrosome. It is involved in binding to the oocyte zona pellucida. In addition, Zpbp2 is located in a conserved 200 kb asthma-associated locus. The Zpbp2 promoter overlaps with an enhancer region affecting expression of Ormdl3 (ORM1-like 3) a sphingolipid biosynthesis regulator. ORMDL3 is associated with endoplasmic reticulum stress and smooth muscle contraction. This targeted mutation deletes exons 1-3, removing part of the promoter/enhancer region affecting expression of both genes.
 
Female mice that are homozygous for the targeted knock-out (KO) mutation are viable and fertile. Homozygous males are subfertile and average 3 pups per litter. Males on a mixed C57BL/6 and 129S7 background exhibit abnormal sperm morphology and a reduced ability of sperm to penetrate the zona pelucida. Sperm morphology has not been examined on the congenic background. Both heterozygote and homozygote KO mice exhibit a gain in DNA methylation at the promoter/enhancer region. In addition to reduced fertility, homozygotes exhibit altered lipid metabolism, decreased levels of docosahexanoic acid (DHA), and increased body weight. Sensitization with ovalbumin results in reduced bronchial reactivity. This strain may be useful for studying male infertility, the regulation of airway hypersensitivity and lipid metabolism.

Zpbp2 (Zona pellucida binding protein) knock-out mice exhibit male infertility, altered lipid metabolism, decreased levels of docosahexanoic acid (DHA), increased body weight and a decreased sensitivity to allergic asthma. This targeted mutation deletes exons 1-3, removing part of the promoter/enhancer region and affecting expression of Zpbp2 and Ormdl3 .

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