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Gene Review

Spam1  -  sperm adhesion molecule 1

Mus musculus

Synonyms: AV039194, Hyal-PH20, Hyaluronidase PH-20, Hyaluronoglucosaminidase PH-20, Ph-20, ...
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Disease relevance of Spam1

  • RESULTS: Examination of the human, mouse and rat SPAM1 loci revealed that transcripts initiate within the pol gene of an endogenous retrovirus (ERV) element [1].

High impact information on Spam1


Biological context of Spam1


Anatomical context of Spam1

  • In wild-type animals, EM studies of in situ transcript hybridization of testis sections and Northern analysis of biochemically fractionated testicular RNA were performed to localize Spam1 transcript [6].
  • Our earlier studies on carriers of spontaneous mutations of mouse Sperm Adhesion Molecule 1 (Spam1) suggested that TRD results from biochemically different sperm, due to a lack of transcript sharing through the intercellular cytoplasmic bridges of spermatids [6].
  • Spam1 RNA was absent from the bridges, associated exclusively with the ER, and was shown to be anchored to the cytoskeleton [6].
  • RPA revealed that Spam1 transcripts are synthesized in a region-dependent manner, with the oviduct having lower transcript levels than the uterus and vagina [7].
  • Here, we report Spam1 RNA and protein expression in the murine vas deferens and efferent ducts [8].

Associations of Spam1 with chemical compounds

  • Mouse epididymal Spam1 (pH-20) is released in the luminal fluid with its lipid anchor [9].
  • Six point mutations were shown to be clustered in the Spam1 hyaluronic acid-binding domain in Rb(6.15) [10].
  • Ultracentrifugation of the luminal fluid reveals that epididymal Spam1 is secreted predominantly as insoluble particles, which when treated with phosphatidylinositol-specific phospholipase C or Triton X-100, reveal that the majority of epididymal Spam1 is released with its lipid anchor, a form in which it can bind to sperm [9].
  • Two-dimensional polyacrylamide gel electrophoresis with immunoblotting reveals one to three isoforms for epididymal Spam1 with the isoelectric point (pl) ranging from 7.3 to 9.0, and four isoforms ranging from 6.6 to 9.0 pl for testicular Spam1 [9].
  • Spam1 on the surface of caudal sperm was shown to mediate the increase in acrosome reactions induced by the synergistic effects of HA and progesterone, as confirmed in sperm from the Rb(6.16) translocation-bearing mice which are Spam1 mutants [11].

Other interactions of Spam1

  • These sperm retained large cytoplasmic droplets engorged with overexpressed Spam1 or Hyal5 protein [6].
  • Interestingly, transcripts for the testicular-type hyaluronidase PH-20 (Spam1, Hyal3) were also detected in normal and autoimmune kidneys as well as in tubular cells and macrophages [12].
  • Using a dual environment culture chamber system in which corpus or cauda epithelial cells are cocultured with their corresponding epididymal fibroblasts in medium supplemented with androgens and epidermal growth factor, we show that in 2- to 6-day cultures Spam1 can be detected immunocytochemically in the epithelial cells [13].

Analytical, diagnostic and therapeutic context of Spam1


  1. Transcription of the human and rodent SPAM1 / PH-20 genes initiates within an ancient endogenous retrovirus. Dunn, C.A., Mager, D.L. BMC Genomics (2005) [Pubmed]
  2. Identification of a hyaluronidase, Hyal5, involved in penetration of mouse sperm through cumulus mass. Kim, E., Baba, D., Kimura, M., Yamashita, M., Kashiwabara, S., Baba, T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. Binding of both acrosome-intact and acrosome-reacted guinea pig sperm to the zona pellucida during in vitro fertilization. Myles, D.G., Hyatt, H., Primakoff, P. Dev. Biol. (1987) [Pubmed]
  4. Epididymal SPAM1 Is a Marker for Sperm Maturation in the Mouse. Chen, H., Griffiths, G., Galileo, D.S., Martin-Deleon, P.A. Biol. Reprod. (2006) [Pubmed]
  5. The mouse Spam1 maps to proximal chromosome 6 and is a candidate for the sperm dysfunction in Rb(6.16)24Lub and Rb(6.15)1Ald heterozygotes. Deng, X., Moran, J., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Primakoff, P., Martin-DeLeon, P.A. Mamm. Genome (1997) [Pubmed]
  6. Spam1-associated transmission ratio distortion in mice: elucidating the mechanism. Martin-DeLeon, P.A., Zhang, H., Morales, C.R., Zhao, Y., Rulon, M., Barnoski, B.L., Chen, H., Galileo, D.S. Reprod. Biol. Endocrinol. (2005) [Pubmed]
  7. Mouse Spam1 (PH-20) is a multifunctional protein: evidence for its expression in the female reproductive tract. Zhang, H., Martin-DeLeon, P.A. Biol. Reprod. (2003) [Pubmed]
  8. Spam1 (PH-20) expression in the extratesticular duct and accessory organs of the mouse: a possible role in sperm fluid reabsorption. Zhang, H., Morales, C.R., Badran, H., El-Alfy, M., Martin-DeLeon, P.A. Biol. Reprod. (2004) [Pubmed]
  9. Mouse epididymal Spam1 (pH-20) is released in the luminal fluid with its lipid anchor. Zhang, H., Martin-Deleon, P.A. J. Androl. (2003) [Pubmed]
  10. Spam1 (PH-20) mutations and sperm dysfunction in mice with the Rb(6.16) or Rb(6.15) translocation. Zheng, Y., Deng, X., Zhao, Y., Zhang, H., Martin-DeLeon, P.A. Mamm. Genome (2001) [Pubmed]
  11. Cytoplasmic localization during testicular biogenesis of the murine mRNA for Spam1 (PH-20), a protein involved in acrosomal exocytosis. Morales, C.R., Badran, H., El-Alfy, M., Men, H., Zhang, H., Martin-DeLeon, P.A. Mol. Reprod. Dev. (2004) [Pubmed]
  12. Expression profile of hyaluronidase mRNA transcripts in the kidney and in renal cells. Sun, L., Feusi, E., Sibalic, A., Beck-Schimmer, B., Wüthrich, R.P. Kidney Blood Press. Res. (1998) [Pubmed]
  13. Mouse epididymal Spam1 (PH-20) is released in vivo and in vitro, and Spam1 is differentially regulated in testis and epididymis. Zhang, H., Martin-DeLeon, P.A. Biol. Reprod. (2001) [Pubmed]
  14. Biochemical maturation of Spam1 (PH-20) during epididymal transit of mouse sperm involves modifications of N-linked oligosaccharides. Deng, X., Czymmek, K., Martin-DeLeon, P.A. Mol. Reprod. Dev. (1999) [Pubmed]
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