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

• RESULTS: In Spink3(-/-) mice, the pancreas developed normally up to 15.5 days after coitus [6].
• CONCLUSIONS: The progressive disappearance of acinar cells in Spink3(-/-) mice was due to autophagic cell death and impaired regeneration [6].
• METHODS: We generated Spink3-deficient (Spink3(-/-)) mice by gene targeting in mouse embryonic stem cells [6].
• The predicted amino acid sequence of p12 shares extensive homology with several members of the Kazal family of secretory protease inhibitors, in particular the pancreatic secretory trypsin inhibitors [7].
• In this study, we demonstrate that the mouse P12 gene promoter specific to the male accessory sex gland can be used to generate transgenic mice that express human growth hormone (hGH) in their seminal vesicle epithelium [8].

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

• Spermatozoa collected from caudal epididymis were devoid of P12 [11].
• The immunohistochemical staining patterns of testis revealed that the P12-binding sites appeared on postmeiotic cells such as spermatids and spermatozoa, but were absent in Leydig cells, Sertoli cells, spermatogonia, and spermatocytes in seminiferous tubules [11].
• Cytochemical study illustrated a P12-binding region on the anterior acrosomes of cells preincubated with P12 [11].
• Concomitantly, as the reversal potential of the inhibitory postsynaptic potential in VPN neurons became more negative, its capacity to deinactivate the LTS increased, and rebound bursts that could maintain oscillations were produced; sustained oscillations became the typical response to internal capsule stimulation at P12 [15].
• A mAb, 10D1, was obtained by fusing spleen cells from BALB/c mice immunized with a CD3/TCR- human T cell line, P12/ichikawa, to mouse myeloma cells, P3X63-Ag8-653 [16].

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

• We examined the developmental profile of a kazal-type trypsin inhibitor (P12) of Mr 6126 in mouse seminal vesicle, characterized its binding sites on the surface of sperm, and assessed its effect on Ca2+ uptake by spermatozoa [11].
• A full length cDNA (MP25) encoding the major mouse prostatic secretory glycoprotein (p25), whose expression is androgen dependent, has been cloned and characterised [21].

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].

References