Issues
EDITORIAL
CLINICAL PUZZLE
Dissecting the phenotypic variability of osteogenesis imperfecta
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.
RESEARCH ARTICLES
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.
Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice
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.
Inhibition of activin A receptor signalling attenuates age-related pathological cardiac remodelling
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.
Characterization of a novel zebrafish model of SPEG-related centronuclear myopathy
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.
Epigenetic downregulation of Socs2 contributes to mutant N-Ras-mediated hematopoietic dysregulation
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.
Modeling the catarrhal stage of Bordetella pertussis upper respiratory tract infections in mice
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.
RESOURCE ARTICLES
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.
Temporal and spatially controlled APP transgene expression using Cre-dependent alleles
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.
Long-term non-invasive drug treatments in adult zebrafish that lead to melanoma drug resistance
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.
Accessible analysis of longitudinal data with linear mixed effects models
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.
FIRST PERSON
Special Issue: The RAS Pathway

Our latest special issue is now complete. It showcases RAS-driven mechanisms of disease progression, and highlights approaches to treat and modify the disease course in model systems.
Call for papers: Moving Heart Failure to Heart Success

Disease Models & Mechanisms is pleased to welcome submissions for consideration for an upcoming special issue, Moving Heart Failure to Heart Success: Mechanisms, Regeneration & Therapy. Submission deadline: 4 July 2022.
Propose a new Workshop

Our Workshops bring together leading experts and early-career researchers from a range of scientific backgrounds. Applications are now open to propose Workshops for 2024, one of which will be held in a Global South country. .
A focus on Drosophila

In a series of front section articles, DMM is highlighting the versatility, breadth, and scope of Drosophila research in human disease modelling and translational medicine.
Apply for a DMM Conference Travel Grant

Aimed at early-career researchers wanting to attend in-person and virtual meetings, the next application deadline for a DMM Conference Travel Grant is 6 June 2022. Find out more and hear from past recipients about their experience of the grant.