Summary: This Clinical Puzzle analyses the largest public OI database as well as data from animal models to address how type I collagen defects contribute to the phenotypic variability of the brittle bone disease osteogenesis imperfecta.
Itavastatin and resveratrol increase triosephosphate isomerase protein in a newly identified variant of TPI deficiency
Summary: A newly identified triosephosphate isomerase (TPI) variant (TPIQ181P) confers TPI deficiency, suggests a molecular and genetic model for its pathogenesis, and the potential for therapeutic intervention.
Summary: Osteoblast-lineage specific Sod2 deficiency in mice leads to increased mtROS, impaired osteoblast function, increased adipogenesis, increased osteoclast activity and increased osteoblast senescence, resulting in bone loss.
Endometrial organoids derived from Mayer–Rokitansky–Küster–Hauser syndrome patients provide insights into disease-causing pathways
Summary: Müllerian agenesis is highly understudied due to the lack of experimental model systems. We close a significant gap by providing the first patient-derived organoid model of diseased tissue.
TOR signalling is required for host lipid metabolic remodelling and survival following enteric infection in Drosophila
Summary: Enteric infection in Drosophila leads to increased TOR signalling, which is required to prevent excess wasting of fat stores and promote survival.
A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infection
Summary: Genes implicated in host survival to Candida albicans infection reveal the role of fucosylation in the turnover and/or stability of proteins required for host defence after immune challenge.
Summary: Attenuated DNA repair is associated with pathological cardiac remodelling and gene expression. Much of this phenotype is attenuated by inhibition of the activin signalling pathway using soluble activin receptor treatment.
Summary: We created a novel zebrafish Speg mutant model of centronuclear myopathy that recapitulates key features of the human disorder and provides insight into pathomechanisms of the disease.
Subcellular localization of mutant P23H rhodopsin in an RFP fusion knock-in mouse model of retinitis pigmentosa
Summary: A mouse line with a knock-in of the human rhodopsin gene altered to contain the P23H mutation and a red fluorescent protein fusion provides a new model for autosomal-dominant retinitis pigmentosa.
Rapid assessment of the temporal function and phenotypic reversibility of neurodevelopmental disorder risk genes in Caenorhabditis elegans
Summary: We identified diverse temporal functional windows and phenotypic reversibility profiles for three neurodevelopmental disorder risk genes: EBF3•unc-3, BRN3A•unc-86 and DYNC1H1•dhc-1. Re-expression of certain genes could rescue multiple phenotypes later in life, prioritizing them for study.
Summary: Jak2/Stat5 is often considered to be parallel to or upstream of Ras signaling. We have discovered a novel signaling feedback loop whereby hyperactive Ras signaling activates Jak2/Stat5 via suppression of Socs2.
Summary: Mouse model of the highly infectious catarrhal stage of pertussis that restricts Bordetella pertussis infection to the upper respiratory tract and exhibits nasopharyngeal inflammation and high levels of shedding.
Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models
Summary: Stool is a readily available, noninvasive and sensitive source of DNA for monitoring repeat expansion in mouse models of four different repeat expansion diseases.
Summary: We describe two strategies and a new mouse allele for improved spatial and temporal control over transgene expression using Cre/CreER drivers in models of Alzheimer's disease and other neurodegenerative disorders.
Summary: We developed a precise drug-pellet dosing method for adult zebrafish melanoma models that can be widely applied to drug discovery in adult zebrafish.
Summary: Using example data in the public domain and a newly developed, accessible web-based analysis tool, linear mixed effects models are demonstrated to be more appropriate for analyzing longitudinal data than ANOVA.