Anti-Collagen IV polyclonal antibody [Biotin]

Salen with two aza-crown ether pendants H2L1 and its analogues H2L2--H2L4 were successfully synthesized starting from benzo-10-aza-15-crown-5 (BN15C5) or morpholine. Their structures were characterized by IR, MS, H-1 NMR and elemental analysis, and were confirmed by X-ray diffraction analysis of H2L1. Moreover, the saturated oxygen uptake of their cobalt(II) complexes CoL1-CoL4 in diethyleneglycol dimethyl ether was determined at different temperature. The oxygenation contants ( K-O2) and thermodynamic parameters (DeltaHdegrees and DeltaSdegrees) were calculated. The modulation of O-2-binding capabilities by pendant substituents were investigated as compared with the parent Schiff base complex CoL5 (CoSalen). The results indicate that the dioxygen affinities of CoL have been much more enhanced by aza-crown pendants than that by morpholino pendants, and the O-2-binding capabilities of CoL1 and CoL2 with aza-crown pendants would also be enhanced by adding alkali metal cations.

Pierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin beta 2 (LAMB2), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation, LAMB2-S80R, which was discovered in a patient with Pierson syndrome and unusually late onset of proteinuria. Biochemical data indicated that this mutation impairs laminin polymerization, which we hypothesized to be the cause of the patient's nephrotic syndrome. Testing this hypothesis in genetically altered mice showed that the corresponding amino acid change (LAMB2-S83R) alone is not pathogenic. However, expression of LAMB2-S83R significantly increased the rate of progression to kidney failure in a Col4a3(-/-) mouse model of autosomal recessive Alport syndrome and increased proteinuria in Col4a5(+/-) females that exhibit a mild form of X-linked Alport syndrome due to mosaic deposition of collagen alpha 3 alpha 4 alpha 5(IV) in the GBM. Collectively, these data show the pathogenicity of LAMB2-S80R and provide the first evidence of genetic modification of Alport phenotypes by variation in another GBM component. This finding could help explain the wide range of Alport syndrome onset and severity observed in patients with Alport syndrome, even for family members who share the same COL4 mutation. Our results also show the complexities of using model organisms to investigate genetic variants suspected of being pathogenic in humans.