Anti-ANPEP monoclonal antibody, clone R3-63 [R-PE]

Most reproductive traits have low heritability and are greatly affected by environmental factors. Teat number and litter size are traits related to the reproduction ability of pigs. To identify quantitative trait loci (QTLs) for teat number traits, a genome-wide association study (GWAS) was conducted using an F-2 intercross between Landrace and Korean native pigs. Genotype analysis was performed using the porcine SNP 60 K beadchip. The GWAS was performed using a mixed-effects model and linear regression approach. When a genome-wide threshold was determined using the Bonferroni method (P = 1.61 x 10(-6)), 38 single nucleotide polymorphism (SNP) markers in pig chromosome 7 (SSC7) were significantly associated with three teat number traits (total teat number, left teat number, and right teat number). Among these, SNPs in 5 genes (HDDC3, LOC100156276, LOC100155863, ANPEP, SCAMP2) were selected for further study based primarily on their statistical significance. A significant association was detected in SCAMP2 g.25280 G>A for total teat number (P = 2.0 x 10(-12)), HDDC3 g. 1319 G>A SNP for left teat number (P = 2.3 x 10(-7)), and SCAMP2 g.14198 G>A for right teat number (P = 4.7 x 10(-12)). These results provide valuable information about the selective breeding for desirable teat numbers in pigs.

Aminopeptidase N/CD13 (Anpep) is a membrane-bound protein that catalyzes the formation of natriuretic hexapeptide angiotensin IV (ANG IV) from ANG III. We previously reported that Anpep is more highly expressed in the kidneys of Dahl salt-resistant (SR/Jr) than salt-sensitive (SS/Jr) rats, Anpep maps to a quantitative trait locus for hypertension, and that the Dahl SR/Jr rat contains a functional polymorphism of the gene. This suggests that renal Anpep may be linked to salt sensitivity; however, its effect on renal Na handling has not been determined. Here, we examined regulation of basolateral Na+ -K+ -ATPase, a preeminent basolateral Na+ transporter in proximal tubule cells, by Anpep in LLC-PK1 cells. Treatment of the cells with Anpep siRNA increased total cellular Na+ -K+ -ATPase activity and basolateral Na+ -K+ -ATPase abundance by approximately twofold. Conversely, Anpep overexpression reduced Na+ -K+ -ATPase activity and basolateral abundance by similar to 50%. Similar effects were observed after treatment with ANG IV (10 nM, x30 min and 12 h). ANG IV receptor (AGTRIV) knockdown via specific siRNA relieved the decreases in basolateral Na+ -K+ -ATPase levels and activity induced by Anpep overexpression. In sum, these results demonstrate that Anpep reduces basolateral Na+ -K+ -ATPase levels via ANG IV/AGTRIV signaling. This novel pathway may be important in renal adaptation to high salt.