Anti-GH1 monoclonal antibody, clone FQS0635

Isolated growth hormone deficiency type II (IGHD2) is mainly caused by heterozygous splice-site mutations in intron 3 of the GH1 gene. A dominant-negative effect of the mutant GH lacking exon 3 on wild-type GH secretion has been proposed; however, the molecular mechanisms involved are elusive. To uncover the molecular systems underlying GH deficiency in IGHD2, we established IGHD2 model mice, which carry both wild-type and mutant copies of the human GH1 gene, replacing each of the endogenous mouse Gh loci. Our IGHD2 model mice exhibited growth retardation along with intact cellular architecture and mildly activated endoplasmic reticulum stress in the pituitary gland, caused by decreased GH-releasing hormone receptor (Ghrhr) and Gh gene promoter activities. Decreased Ghrhr and Gh promoter activities were likely caused by reduced levels of nuclear CREB3L2, which was demonstrated to stimulate Ghrhr and Gh promoter activity. To our knowledge, this is the first in vivo study to reveal a novel molecular mechanism of GH deficiency in IGHD2, representing a new paradigm that differs from widely accepted models.

Main conclusion The screening of rice mutants with improved cellulose to glucose saccharification efficiency (SE) identifies reduced xylan and/or ferulic acid, and a qualitative change of lignin to impact SE. To ensure the availability of sustainable energy, considerable effort is underway to utilize lignocellulosic plant biomass as feedstock for the production of biofuels. However, the high cost of degrading plant cell wall components to fermentable sugars (saccharification) has been problematic. One way to overcome this barrier is to develop plants possessing cell walls that are amenable to saccharification. In this study, we aimed to identify new molecular factors that influence saccharification efficiency (SE) in rice. By screening 22 rice mutants, we identified two lines, 122 and 108, with improved SE. Reduced xylan and ferulic acid within the cell wall of line 122 were probable reasons of improved SE. Line 108 showed reduced levels of thioglycolic-released lignin; however, the amount of Klason lignin was comparable to the wild-type, indicating that structural changes had occurred in the 108 lignin polymer which resulted in improved SE. Positional cloning revealed that the genes responsible for improved SE in 122 and 108 were rice CONSTITUTIVE PHOTO-MORPHOGENIC 1 (OsCOP1) and GOLD HULL AND INTERNODE 1 (GH1), respectively, which have not been previously reported to influence SE. The screening of mutants for improved SE is an efficient approach to identify novel genes that affect SE, which is relevant in the development of crops as biofuel sources.