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Open AccessMeCP2 binds to methylated DNA independently of phase separation and heterochromatin organisation
Correlative evidence has suggested that the methyl-CpG-binding protein MeCP2 contributes to the formation of heterochromatin condensates via liquid-liquid phase separation. This interpretation has been reinfor...
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Open AccessProtein citrullination and NET formation do not contribute to the pathology of A20/TNFAIP3 mutant mice
A20 serves as a critical brake on NF-κB-dependent inflammation. In humans, polymorphisms in or near the TNFAIP3/A20 gene have been linked to various inflammatory disorders, including systemic lupus erythematosus ...
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Open AccessOTULIN protects the intestinal epithelium from apoptosis during inflammation and infection
The intestinal epithelium is a single cell layer that is constantly renewed and acts as a physical barrier that separates intestinal microbiota from underlying tissues. In inflammatory bowel disease (IBD) in h...
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Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements
Accurate somatic mutation detection from single-cell DNA sequencing is challenging due to amplification-related artifacts. To reduce this artifact burden, an improved amplification technique, primary template-...
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Open AccessInnovative mouse models for the tumor suppressor activity of Protocadherin-10 isoforms
Nonclustered mouse protocadherin genes (Pcdh) encode proteins with a typical single ectodomain and a cytoplasmic domain with conserved motifs completely different from those of classic cadherins. Alternative spli...
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Open AccessOTULIN maintains skin homeostasis by controlling keratinocyte death and stem cell identity
OTULIN is a deubiquitinase that specifically cleaves linear ubiquitin chains. Here we demonstrate that the ablation of Otulin selectively in keratinocytes causes inflammatory skin lesions that develop into verruc...
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Open AccessRing finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity
ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we use a v...
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Open AccessResponse to correspondence on “Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation”
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Two distinct ubiquitin-binding motifs in A20 mediate its anti-inflammatory and cell-protective activities
Protein ubiquitination regulates protein stability and modulates the composition of signaling complexes. A20 is a negative regulator of inflammatory signaling, but the molecular mechanisms involved are ill und...
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Open AccessReproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation
CRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study re...
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Open AccessNovel strategy for rapid functional in vivo validation of oncogenic drivers in haematological malignancies
In cancer research, it remains challenging to functionally validate putative novel oncogenic drivers and to establish relevant preclinical models for evaluation of novel therapeutic strategies. Here, we descri...
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Open AccessA new mouse model to study the role of ectopic Nanos3 expression in cancer
NANOS3 is a gene conserved throughout evolution. Despite the quite low conservation of Nanos sequences between different organisms and even between Nanos paralogs, their role in germ cell development is remarkabl...
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Open AccessA knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8
Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot–Marie–Tooth disease, and recently distal myopathy. It is so far not clear how ...
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Open AccessOverexpression of Glucocorticoid-induced Leucine Zipper (GILZ) increases susceptibility to Imiquimod-induced psoriasis and involves cutaneous activation of TGF-β1
Psoriasis vulgaris is a chronic inflammatory skin disease affecting millions of people. Its pathophysiology is complex and involves a skin compartment with epidermal and immune cells which produce cytokines, e...
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Open AccessCardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice
Oxidative stress, a central mediator of cardiovascular disease, results in loss of the prosthetic haem group of soluble guanylate cyclase (sGC), preventing its activation by nitric oxide (NO). Here we introduc...
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Open AccessEfficient and User-Friendly Pluripotin-based Derivation of Mouse Embryonic Stem Cells
Classic derivation of mouse embryonic stem (ES) cells from blastocysts is inefficient, strain-dependent, and requires expert skills. Over recent years, several major improvements have greatly increased the suc...
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Open AccessNO-insensitive sGCbeta1 H105F knockin mice: if NO has no place to go
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Open AccessTargeting the NO – cGMP pathway: phenoty** of NO-insensitive sGCbeta1 H105F knockin mice
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Open AccessTransgenic mice with a NO-insensitive soluble guanylate cyclase
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Caspase-14 protects against epidermal UVB photodamage and water loss
Caspase-14 belongs to a conserved family of aspartate-specific proteinases. Its expression is restricted almost exclusively to the suprabasal layers of the epidermis and the hair follicles1,2,3,4. Moreover, the p...