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Gene Review

Spink3  -  serine peptidase inhibitor, Kazal type 3

Mus musculus

Synonyms: P12, Prostatic secretory glycoprotein, Serine protease inhibitor Kazal-type 3, p12, prostatic secretory glycoprotein
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Disease relevance of Spink3

  • P12 antigen is represented on a wide range of cell lines and tissues, including a subset of teratocarcinomas [1].
  • TNF-alpha-/- and WT mice showed a similar sensitivity to hyperoxia-induced retinal ischemia at P12 [2].
  • RESULTS: alpha(v)-integrin expression started immediately after induction of hypoxia (at postnatal day 12, p12) and persisted only during the initial period of neovascularization (until day p14) [3].
  • Mutant virions in which MA was not cleaved from p12 were still infectious, with a specific infectivity only approximately 10-fold below that of the wild type [4].
  • Amino acid sequence and structural properties of protein p12, an African swine fever virus attachment protein [5].

High impact information on Spink3


Chemical compound and disease context of Spink3

  • The COX-2 inhibitor, rofecoxib (15 mg/kg body weight intraperitoneally) was administered to normal and ROP mice from P12 to P17 [9].

Biological context of Spink3

  • Defbeta1 and Spink3 are both upregulated by E2+P, whereas INDO and GPR105 have a complementary profile of upregulation by E2 alone and suppression of the E2 effect by P [10].
  • Analysis of equilibrium data from the binding assay using 125I-P12 with a Scatchard plot showed a single type of P12-binding sites on sperm, with an apparent dissociation constant of 70.15 +/- 5.25 nM and the capacity of 1.49 +/- 0.06 x 10(6) binding sites/cell [11].
  • We have used biolistic transfection of organotypic slices of P12 cerebellum to identify a 40-bp element from the calbindin promoter that is necessary and sufficient for Purkinje cell specific expression in this transient in situ assay [12].
  • To study the molecular mechanisms involved in this model of cell-specific control of gene expression, we cloned fragments containing various lengths of the p12 promoter upstream of the CAT reporter gene [13].
  • We noticed that B cell receptor ligation or phorbol 12-myristate 13-acetate treatment induced intracellular vesicles containing major histocompatibility complex (MHC) class II and invariant chain (Ii), and increased the amount of transmembrane p12 Ii fragments coimmunoprecipitated with class II molecules [14].

Anatomical context of Spink3


Associations of Spink3 with chemical compounds

  • The NMDA/non-NMDA ratio was similar at P7, P21, and P40, but showed a clear peak at P12 [17].
  • Myelination was enhanced and ventriculomegaly reduced in hypoxia-exposed neonatal pups treated with caffeine from P3 to P12 [18].
  • Mice exposed to hyperoxia for 5 days starting at postnatal day 7 (P7) and returned to room air (at P12) showed closure of the central retinal vasculature [19].
  • Half of each WT litter was treated with the cytokine inhibitor semapimod (formerly known as CNI-1493) (5 mg/kg) by daily intraperitoneal injection from the time of reintroduction to room air at P12 until P17 [2].
  • Analysis of the chondroitinase digestion products revealed that GlcA beta 1-3GalNAc(4S) disaccharide unit (A unit) was the major component in these preparations and that PG-P20 contained 1.3% D unit, which was not detected in PG-P7 and PG-P12 [20].

Other interactions of Spink3


Analytical, diagnostic and therapeutic context of Spink3

  • Castration of adult mice resulted in cessation of P12 expression [11].
  • The tumor-targeting properties of F16 and P12 were assessed by biodistribution studies in tumor xenografts using the antibodies in small immunoprotein (SIP) format [22].
  • Real-time quantitative PCR experiments indicated that tomosyn-1 expression was up-regulated less than threefold between developmental stages E10 and P12, whereas tomosyn-2 expression increased 31-fold [23].
  • Whole cell recordings of evoked excitatory postsynaptic currents (EPSCs) and immunohistochemistry of GluR1-4 subunits were performed using brain stem slices from congenitally deaf or hearing mice at postnatal days P5 and P12 [24].
  • The presence in infected AGC of defective LP-BM5 MuLV genome, a critical component for induction of the disease referred to as murine AIDS, was confirmed by Southern blot hybridization using a probe reactive with the p12 gag sequence of the 4.9 kb defective genome [25].


  1. High-molecular-weight glycoproteins of human teratocarcinoma defined by monoclonal antibodies to carbohydrate determinants. Rettig, W.J., Cordon-Cardo, C., Ng, J.S., Oettgen, H.F., Old, L.J., Lloyd, K.O. Cancer Res. (1985) [Pubmed]
  2. Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy. Gardiner, T.A., Gibson, D.S., de Gooyer, T.E., de la Cruz, V.F., McDonald, D.M., Stitt, A.W. Am. J. Pathol. (2005) [Pubmed]
  3. Kinetics of integrin expression in the mouse model of proliferative retinopathy and success of secondary intervention with cyclic RGD peptides. Chavakis, E., Riecke, B., Lin, J., Linn, T., Bretzel, R.G., Preissner, K.T., Brownlee, M., Hammes, H.P. Diabetologia (2002) [Pubmed]
  4. Effects of blocking individual maturation cleavages in murine leukemia virus gag. Oshima, M., Muriaux, D., Mirro, J., Nagashima, K., Dryden, K., Yeager, M., Rein, A. J. Virol. (2004) [Pubmed]
  5. Amino acid sequence and structural properties of protein p12, an African swine fever virus attachment protein. Alcamí, A., Angulo, A., López-Otín, C., Muñoz, M., Freije, J.M., Carrascosa, A.L., Viñuela, E. J. Virol. (1992) [Pubmed]
  6. Autophagic cell death of pancreatic acinar cells in serine protease inhibitor Kazal type 3-deficient mice. Ohmuraya, M., Hirota, M., Araki, M., Mizushima, N., Matsui, M., Mizumoto, T., Haruna, K., Kume, S., Takeya, M., Ogawa, M., Araki, K., Yamamura, K. Gastroenterology (2005) [Pubmed]
  7. A secretory protease inhibitor requires androgens for its expression in male sex accessory tissues but is expressed constitutively in pancreas. Mills, J.S., Needham, M., Parker, M.G. EMBO J. (1987) [Pubmed]
  8. Seminal vesicle production and secretion of growth hormone into seminal fluid. Dyck, M.K., Gagné, D., Ouellet, M., Sénéchal, J.F., Bélanger, E., Lacroix, D., Sirard, M.A., Pothier, F. Nat. Biotechnol. (1999) [Pubmed]
  9. COX-2 inhibition and retinal angiogenesis in a mouse model of retinopathy of prematurity. Wilkinson-Berka, J.L., Alousis, N.S., Kelly, D.J., Gilbert, R.E. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  10. Development of a mouse model of mammary gland versus uterus tissue selectivity using estrogen- and progesterone-regulated gene markers. Crabtree, J.S., Zhang, X., Peano, B.J., Zhang, Z., Winneker, R.C., Harris, H.A. J. Steroid Biochem. Mol. Biol. (2006) [Pubmed]
  11. Developmental profile of a caltrin-like protease inhibitor, P12, in mouse seminal vesicle and characterization of its binding sites on sperm surface. Chen, L.Y., Lin, Y.H., Lai, M.L., Chen, Y.H. Biol. Reprod. (1998) [Pubmed]
  12. A calcium responsive element that regulates expression of two calcium binding proteins in Purkinje cells. Arnold, D.B., Heintz, N. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  13. Identification of a DNA-binding site for the transcription factor GC2 in the promoter region of the p12 gene and repression of its positive activity by upstream negative regulatory elements. Guérin, S.L., Pothier, F., Robidoux, S., Gosselin, P., Parker, M.G. J. Biol. Chem. (1990) [Pubmed]
  14. Selective modulation of the major histocompatibility complex class II antigen presentation pathway following B cell receptor ligation and protein kinase C activation. Barois, N., Forquet, F., Davoust, J. J. Biol. Chem. (1997) [Pubmed]
  15. Maturation of neuronal form and function in a mouse thalamo-cortical circuit. Warren, R.A., Jones, E.G. J. Neurosci. (1997) [Pubmed]
  16. A novel homodimeric molecule involved in human T cell activation. Kobata, T., Yagita, H., Matsuda, H., Tansyo, S., Yakura, H., Katagiri, M., Okumura, K. J. Immunol. (1990) [Pubmed]
  17. Developmental profile of the changing properties of NMDA receptors at cerebellar mossy fiber-granule cell synapses. Cathala, L., Misra, C., Cull-Candy, S. J. Neurosci. (2000) [Pubmed]
  18. Protective effects of caffeine on chronic hypoxia-induced perinatal white matter injury. Back, S.A., Craig, A., Ling Luo, N., Ren, J., Akundi, R.S., Ribeiro, I., Rivkees, S.A. Ann. Neurol. (2006) [Pubmed]
  19. The 67-kd laminin receptor is preferentially expressed by proliferating retinal vessels in a murine model of ischemic retinopathy. Stitt, A.W., McKenna, D., Simpson, D.A., Gardiner, T.A., Harriott, P., Archer, D.B., Nelson, J. Am. J. Pathol. (1998) [Pubmed]
  20. Heterogeneity of the chondroitin sulfate portion of phosphacan/6B4 proteoglycan regulates its binding affinity for pleiotrophin/heparin binding growth-associated molecule. Maeda, N., He, J., Yajima, Y., Mikami, T., Sugahara, K., Yabe, T. J. Biol. Chem. (2003) [Pubmed]
  21. Androgen regulated expression of a spermine binding protein gene in mouse ventral prostate. Mills, J.S., Needham, M., Parker, M.G. Nucleic Acids Res. (1987) [Pubmed]
  22. Tumor-targeting properties of novel antibodies specific to the large isoform of tenascin-C. Brack, S.S., Silacci, M., Birchler, M., Neri, D. Clin. Cancer Res. (2006) [Pubmed]
  23. Two distinct genes drive expression of seven tomosyn isoforms in the mammalian brain, sharing a conserved structure with a unique variable domain. Groffen, A.J., Jacobsen, L., Schut, D., Verhage, M. J. Neurochem. (2005) [Pubmed]
  24. Development of a robust central auditory synapse in congenital deafness. Youssoufian, M., Oleskevich, S., Walmsley, B. J. Neurophysiol. (2005) [Pubmed]
  25. Central nervous system infection in a murine retrovirus-induced immunodeficiency syndrome. Sei, Y., Makino, M., Vitković, L., Chattopadhyay, S.K., Hartley, J.W., Arora, P.K. J. Neuroimmunol. (1992) [Pubmed]
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