Issues
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Cover image
Cover Image
Cover: X-linked infantile spasms syndrome (ISSX) is a severe developmental epileptic encephalopathy featuring infantile spasms beginning early in life. Genetic mouse models such as Arx(GCG)10+7 recapitulate human mutations found in ISSX and are crucial for investigating the impact of these mutations on neonatal brain development. Postnatal analysis of neocortex in Arx(GCG)10+7 revealed exaggerated apoptosis at the onset of spasms in this model; however, apoptosis did not affect Arx-expressing or other cortical neurons. Pictured is a brain slice from a 14-day-old mutant Arx(GCG)10+7 mouse, showing Arx protein (green), cortical neurons (red) and nuclei (DAPI; blue). See article by Siehr et al. (dmm042515). Cover image is licensed under a Creative Commons Attribution 4.0 International license.
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Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells
Summary: Here, we generated a GNRH1-reporter cell line in hPSCs and investigated transcriptomes of GNRH1-expressing neurons and their progenitors, potentially leading to validation of new genes related to GnRH neuron function.
FX11 limits Mycobacterium tuberculosis growth and potentiates bactericidal activity of isoniazid through host-directed activity
Summary: Targeting LDHA results in tumor regression in experimental models. Likewise, co-administration of a known small molecule LDHA inhibitor and an anti-tuberculosis drug has improved the tuberculosis therapeutic outcomes in murine models.
Genetic background modifies phenotypic severity and longevity in a mouse model of Niemann-Pick disease type C1
Summary: This study identifies genomic regions in a new Npc1 mutant mouse model containing potential modifier variants associated with changes in phenotypic severity and lifespan.
Inactivation of Zeb1 in GRHL2-deficient mouse embryos rescues mid-gestation viability and secondary palate closure
Summary: Epithelial transcription factor GRHL2 is required for face closure while mesenchymal transcription factor ZEB1 is required for palate closure. Surprisingly, animals lacking both factors close their face and secondary palate.
Control of translation elongation in health and disease
Summary: In this Review, we outline the process of elongation and discuss the relative contributions of transfer RNAs, elongation factors and their modifiers to this process, and how their dysregulation contributes towards disease.
A murine model demonstrates capsule-independent adaptive immune protection in survivors of Klebsiella pneumoniae respiratory tract infection
Summary: This novel mouse model of nonlethal pulmonary Klebsiella pneumoniae infection allows for the exploration of mechanisms required to mount a protective memory response to K. pneumoniae in the lung.
Zebrafish models of sarcopenia
Summary: Zebrafish and other small fish have become powerful disease models. Here, we summarize the evidence for the utility of small teleost models for genetic research in sarcopenia – the age-related loss of muscle mass and function.
Arx expansion mutation perturbs cortical development by augmenting apoptosis without activating innate immunity in a mouse model of X-linked infantile spasms syndrome
Editor's choice: We found non-cell-autonomous apoptosis and fewer Arx+ interneurons in neonatal neocortex of an X-linked infantile spasms syndrome Arx expansion model. Early estradiol therapy rescued Arx+ interneuron density, but did not prevent apoptosis.
Six1 proteins with human branchio-oto-renal mutations differentially affect cranial gene expression and otic development
Summary: Branchio-otic/branchio-oto-renal syndromes result in craniofacial defects including deafness. Four of the known human SIX1 mutations cause differential changes in craniofacial gene expression and otic morphology when expressed in Xenopus embryos.
Virtual Meeting - Developmental Disorders: From Mechanism to Treatment
A collaboration between the Development and Disease Models & Mechanisms journal teams, this virtual Meeting will unite developmental biologists, human geneticists and clinical researchers to focus on building bridges from bench to clinic. Register your interest and find out more.
High-dose vitamin B1 therapy prevents the development of experimental fatty liver driven by overnutrition
Vitamin B1 is shown to prevent nutrition-induced fatty liver in our current Editor’s choice by Hay Davir and his colleagues, when they use sheep as a large-animal model for studying the disease.
Find out more in an interview with the paper's first authors, Mugagga Kalyesubula and Ramgopal Mopuri.
Upcoming grant deadlines
Grants awarded by The Company of Biologists help scientists travel, attend events and host sustainable activities. Make a note of the upcoming application deadlines and find out more about the grants on offer:
DMM Conference Travel Grants
17 May 2021
Sustainable Conferencing Grants
17 May 2021
Travelling Fellowships
31 May 2021
Scientific Meeting Grants
4 June 2021
Call for papers - The RAS Pathway: Diseases, Therapeutics and Beyond
Our upcoming special issue is welcoming submissions until 3 May 2021. Guest-edited by Donita Brady (Perelman School of Medicine at the University of Pennsylvania, USA) and Arvin Dar (Icahn School of Medicine at Mount Sinai, USA), the issue will focus on targeting the RAS pathway.