Anti-TNFRSF11B monoclonal antibody, clone FQS4603

Most patients with juvenile Paget's disease (JPD) are homozygous for mutations in the gene TNFRSF11B that result in deficiency of osteoprotegerin (OPG) a key regulator of bone turnover. So far, about 10 different OPG mutations have been described. The current study presents two novel OPG mutations in JPD patients. Patient 1 was diagnosed at the age of 9 months when he presented with inability to sit up, slow growth, marked bone pain and very high levels of serum alkaline phosphatase. Patient 2 presented a milder phenotype. He was initially diagnosed with osteogenesis imperfecta, and although he had numerous fractures and bone deformity, he was still independently mobile at the age of 19 years, when a diagnosis of JPD was confirmed. Sequence analysis of DNA samples from the patients determined two novel homozygous mutations in TNFSRF11B. Patient 1 (severe phenotype) had a large (245-251 kbp) homozygous deletion beginning in intron 1 that resulted in loss of 4 of the 5 exons of TNFSRF11B, including the whole ligand-binding domain. Patient 2 had a homozygous missense mutation resulting in a Thr > Pro change in exon 2 of TNFSRF11B that is predicted to disrupt the OPG ligand-binding domain. Taken in conjunction with other published cases, these results are consistent with the hypothesis that the most severe phenotypes in JPD are seen in patients with major gene deletions or mutations affecting cysteine residues in the ligand-binding domain. (C) 2014 Elsevier Inc. All rights reserved.

Improvements on growth and carcass traits in the poultry industry have been achieved by intense selection for heavier chickens at early ages. This faster growth has caused serious problems due to insufficient skeletal structure development needed to support the musculature of modern broilers. The osteoprotegerin gene (OPG), located on GGA2, is an important regulator of bone metabolism and reabsorption, being suggestive as a possible functional candidate gene associated with bone integrity in chickens. This study reports associations of a single nucleotide polymorphism (SNP) in the OPG gene with production traits in a parental broiler line. Different phenotypic groups were evaluated: performance, carcass and skeletal traits. SNPs were identified within the OPG gene and the most informative SNP g.9144C > G was chosen for association analyses. Chickens (n = 1230) were genotyped using PCR-RFLP. The association was carried out with QxPaK v4.0 software using a mixed model including sex, hatch and SNP as fixed effects, and the infinitesimal and residual as random effects. The OPG SNP was associated with important traits as body weight at 21 days, weights of tibia and drumstick skin, leg muscle yield, and tibia breaking strength (P < 0.05). Associations were explained by the additive effect of the SNP and the additive effect within sex. This SNP could be considered a potential marker to improve bone resistance in chickens; however, caution should be taken because of its negative effect in other important traits evaluated in this study. Furthermore, these findings suggest a possible involvement of the OPG gene in fat deposition in poultry.