Summary: This Perspective discusses the special features that make it challenging to develop new therapies for pediatric cancers, and the ways in which collaboration centered on improved models can meet these challenges.
Summary: Current animal models of bronchopulmonary dysplasia suffer from a lack of standardization, which hampers the translational relevancy of findings. Here the current state of available models is reviewed, offering recommendations for improvement.
Summary: In this Review, we discuss the in vivo and in vitro models available to study AIRE deficiency, and how they may contribute to restoring immunological tolerance in APECED patients.
The infantile myofibromatosis NOTCH3 L1519P mutation leads to hyperactivated ligand-independent Notch signaling and increased PDGFRB expression
Summary: Analysis of the L1519P mutation in NOTCH3 and the relationship between Notch and PDGF signaling in infantile myofibromatosis revealed that NOTCH3L1519P generates hyperactivated, ligand-independent Notch signaling, which acts epistatically over PDGF signaling.
Altered cytoskeletal arrangement in induced pluripotent stem cells and motor neurons from patients with riboflavin transporter deficiency
Summary: This study deals with pathomechanisms underlying riboflavin transporter deficiency, a rare recessively inherited early-onset neurodegenerative condition. Using patient-derived iPSCs, we report on cytoskeletal abnormalities, which are reverted by combined riboflavin/antioxidant treatment.
Cardiovascular phenotype of the Dmdmdx rat – a suitable animal model for Duchenne muscular dystrophy
Summary: We characterized the cardiovascular abnormalities of Dmdmdx rats, demonstrating that Dmdmdx rats show similar cardiac and vascular endothelial function impairments to Duchenne muscular dystrophy patients, representing a model of the dystrophic heart.
Summary: We observed that Lmx1b mutant mice of different strain backgrounds vary in onset and severity of glaucoma-related phenotypes and identified a modifier locus on Chr 18. These results could increase understanding of the mechanisms underlying glaucoma.
A muscle growth-promoting treatment based on the attenuation of activin/myostatin signalling results in long-term testicular abnormalities
Editor’s choice: Brief exposure of the mouse testis to a muscle growth-promoting molecule initiates a cascade of molecular changes that expands over time, even when the treatment has stopped.
Inducible expression of human C9ORF72 36× G4C2 hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice
Summary: Only 36 C9ORF72 repeats are sufficient for RAN translation in a new mouse model for amyotrophic lateral sclerosis and frontotemporal dementia. Reducing toxic dipeptides can prevent but not reverse the phenotype.
Hearing impairment due to Mir183/96/182 mutations suggests both loss-of-function and gain-of-function effects
Summary: Our study describes mice carrying knockout alleles of microRNAs involved in hearing and suggests that a point mutation in a microRNA can have a greater phenotypic impact than a null allele.
RET inhibition in novel patient-derived models of RET fusion- positive lung adenocarcinoma reveals a role for MYC upregulation
Summary: Establishment of four patient-derived models of RET fusion-positive lung adenocarcinomas with three different RET fusions shows that MYC expression is regulated by RET.
Neural crest-specific loss of Bmp7 leads to midfacial hypoplasia, nasal airway obstruction and disordered breathing, modeling obstructive sleep apnea
Summary: Using morphometric, respiratory function and metabolomics analyses, we demonstrate that the Bmp7 neural crest knockout mouse is a model for nasal airway obstruction with a craniofacial origin, allowing the study of disordered breathing.
Summary: We examined the cellular effects of mislocalization of TDP-43, a key pathological protein in amyotrophic lateral sclerosis and frontotemporal dementia, using the eye as a model and demonstrated axonal cytoskeleton alterations.
Disruption of a Hedgehog-Foxf1-Rspo2 signaling axis leads to tracheomalacia and a loss of Sox9+ tracheal chondrocytes
Summary: Genetic and molecular analyses of mutant mouse embryos reveal a HH-Foxf1-Rspo2 signaling axis that informs the mechanistic basis of tracheomalacia in individuals with Hedgehog pathway mutations.
Summary: Analysis of a large library of mouse embryonic stem cell lines with gene trap insertions revealed mutations in 2202 unique non-coding RNA genes, which will significantly contribute to the functional annotation of non-coding RNA genes.