Search

Author(s): D. Holstead Jones [1, 2, 3, 11, 10]; Tomoki Nakashima [1, 11]; Otto H. Sanchez [4, 10]; Ivona Kozieradzki [1, 2, 3]; Svetlana V. Komarova [5]; Ildiko Sarosi [6]; [...]

Results demonstrate that the calcium-sensing protein DREAM is involved in pain processing. Mutants lacking this protein respond poorly to acute thermal, mechanical, and visceral pain as well as to chronic neuropathic and inflammatory pain.

Author(s): Kurt Bachmaier [1]; Connie Krawczyk [1]; Ivona Kozieradzki [1]; Young-Yun Kong [1]; Takehiko Sasaki [1]; Antonio Oliveira-dos-Santos [1]; Sanjeev Mariathasan [2]; Dennis Bouchard [1]; Andrew Wakeham [1]; Annick Itie [...]

Bone resorption and remodeling is a very precisely controlled body process that requires osteoclasts to function as a part of the process. Mice that lack the TNF receptor-associated factor 6 (TRAF6) are osteopetrotic with defects in tooth eruption and bone remodeling, the result of impaired osteoclast activity. TRAF6 has been shown to be crucial in IL-1 and CD40 signaling and also in lipopolysaccharide (LPS) signaling, which would not be expected. It is essential for survival perinatally and postnatally, also unexpected.

The process of morphogenesis and remodelling of bone is controlled physiologically with the synthesis of bone matrix by osteoblasts and resorption of bone by osteoclasts. It has been found that the new TNF-family molecule osteoprotegerin ligand (OPGL) can activate mature osteoclasts and mediate osteoclastogenesis in the presence of colony-stimulating factor-1 (CSF-1). Studies have shown that the molecule is an important factor in early differentiation of thymocytes and B-cell precursors, and opgl-1- mice were found to lack lymph nodes.

Intravenous keratinocyte growth factor (KGF) was shown to stimulate the proliferation of alveolar and bronchial cells in mice and rats. KGF was very effective in preventing experimental bleomycin-induced pulmonary dysfunction, weight loss and mortality in mice and rats. The effectiveness of intravenous KGF in preventing lung injury suggested that the mechanisms of the protective effect of KGF may involve more than pulmonary cell proliferation.

Osteoprotegerin (OPG) plays a critical role in regulating postnatal bone mass. Experiments with OPG deficient mice also indicates a corelation between medial calcification of the aorta and renal arteries and the protein. This association between osteoporosis and arterial calcification opens possibilities for studying the impact of OPG regulation on these problems.

Abstract Background Activating mutations in the KRAS gene occur frequently in human tumors, including colorectal carcinomas; most mutations occur in codons 12 and 13. Mutations in KRAS have been associated with poor response to anti-epidermal growth factor receptor antibodies. Therefore, an accurate and readily available analysis of KRAS mutational status is needed. The aim of this study was to evaluate concordance between KRAS assays performed by 6 different laboratories. Methods Forty formalin-fixed paraffin-embedded colorectal cancer tumor samples were obtained. Sample sections were submitted for KRAS mutation analysis to 5 independent commercial laboratories (Agencourt, Gentris, Genzyme, HistoGeneX, and Invitek) and to the Amgen DNA Sequencing Laboratory for direct polymerase chain reaction sequencing. The assay used by Invitek is no longer commercially available and has been replaced by an alternative technique. Results from the commercial services were compared with those from Amgen direct sequencing by κ statistics. Results KRAS mutations were observed in codon 12 and/or 13 in 20 of 40 (50%) samples in Amgen direct sequencing assays. Results from HistoGeneX (κ = 0.95), Genzyme (κ = 0.94), and Agencourt (κ = 0.94) were in almost perfect agreement with these results, and the results from Gentris were in substantial agreement with the results from Amgen (κ = 0.75). The Invitek allele-specific assay demonstrated slight agreement (κ = 0.13). Conclusions This study provides data on the comparability of KRAS mutational analyses. The results suggest that most (but not all) commercial services provide analysis that is accurate and comparable with direct sequencing.

The article examines how targeted deletion of the sclerostin gene in laboratory mice resulted in increased bone formation and bone strength. Sclerosteosis is a high bone mass genetic abnormality in humans caused by inactivating mutations in SOST, which in the gene encoding sclerostin. Based on this information, sclerostin has become a major negative regulator of bone mass.

Heterotrimeric G proteins of the Gq class have been implicated in signaling pathways regulating cardiac growth under physiological and pathological conditions. Knockout mice carrying inactivating mutations in both of the widely expressed Gα q class genes, Gα q and Gα11, demonstrate that at least two active alleles of these genes are required for extrauterine life. Mice carrying only one intact allele [Gα q(­/+);Gα11(­/­) or Gαq(­/­);Gα11(­/+)] died shortly after birth. These mutants showed a high incidence of cardiac malformation. In addition, Gα q(­/­);Gα11(­/+) newborns suffered from craniofacial defects. Mice lacking both Gα q and Gα11 [Gαq(­/­);Gα11(­/­)] died at embryonic day 11 due to cardiomyocyte hypoplasia. These data demonstrate overlap in Gαq and Gα11 gene functions and indicate that the Gq class of G proteins plays a crucial role in cardiac growth and development. [ABSTRACT FROM AUTHOR]