Mitochondrial Localization and Ocular Expression of Mutant Opa3 in a Mouse Model of 3-Methylglutaconicaciduria Type III

Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the axonal protein neuregulin 1 type III regulate Schwann cell fate and myelination. Here we ask if modulating neuregulin 1 type III levels in neurons would restore myelination in a model of congenital hypomyelinating neuropathy (CHN). Using a mouse model of CHN, we rescued the myelination defects by early overexpression of neuregulin 1 type III. Surprisingly, the rescue was independent from the upregulation of Egr2 or essential myelin genes. Rather, we observed the activation of MAPK/ERK and other myelin genes such as peripheral myelin protein 2 (Pmp2) and oligodendrocyte myelin glycoprotein (Omg). We also confirmed that the permanent activation of MAPK/ERK in Schwann cells has detrimental effects on myelination. Our findings demonstrate that the modulation of axon-to-glial neuregulin 1 type III signaling has beneficial effects and restores myelination defects during development in a model of CHN.

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Type III collagen affects dermal and vascular collagen fibrillogenesis and tissue integrity in a mutant Col3a1 transgenic mouse model

Matrix Biology ◽

10.1016/j.matbio.2018.03.008 ◽

2018 ◽

Vol 70 ◽

pp. 72-83 ◽

Cited By ~ 18

Author(s):

Sanne D'hondt ◽

Brecht Guillemyn ◽

Delfien Syx ◽

Sofie Symoens ◽

Riet De Rycke ◽

...

Keyword(s):

Mouse Model ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Type Iii Collagen ◽

Collagen Fibrillogenesis ◽

Type Iii ◽

Tissue Integrity

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The Actin-Polymerizing Activity of SipA Is Not Essential for Salmonella enterica Serovar Typhimurium-Induced Mucosal Inflammation

Infection and Immunity ◽

10.1128/iai.00337-12 ◽

2013 ◽

Vol 81 (5) ◽

pp. 1541-1549 ◽

Cited By ~ 7

Author(s):

Dongju Li ◽

Xueqin Wang ◽

Lu Wang ◽

Daoguo Zhou

Keyword(s):

Inflammatory Response ◽

Mouse Model ◽

Salmonella Enterica ◽

Intestinal Inflammation ◽

Host Cells ◽

Bacterial Invasion ◽

Content Type ◽

Type Iii ◽

Serovar Typhimurium ◽

Mouse Model Of Infection

ABSTRACTSalmonella entericaserovar Typhimurium depends on type III secretion systems to inject effector proteins into host cells to promote bacterial invasion and to induce intestinal inflammation. SipA, a type III effector, is known to play important roles in both the invasion and the elicitation of intestinal inflammation. The actin-modulating activity of SipA has been shown to promoteSalmonellaentry into epithelial cells. To investigate whether the actin-modulating activity of SipA is required for its ability to induce an inflammatory responsein vivo, we generated the SipAK635A E637Wmutant, which is deficient in actin-modulating activity.Salmonellastrains expressing the chromosomal SipAK635A E637Wpoint mutation had reduced invasion abilities but still caused colitis similar to that caused by the wild-type strain in a mouse model of infection. Our data indicate that the SipA actin-polymerizing activity is not essential for the SipA-induced inflammatory response in the mouse model of infection.

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Peptidoglycan N-Acetylglucosamine Deacetylase, a Putative Virulence Factor in Streptococcus pneumoniae

Infection and Immunity ◽

10.1128/iai.70.12.7176-7178.2002 ◽

2002 ◽

Vol 70 (12) ◽

pp. 7176-7178 ◽

Cited By ~ 82

Author(s):

Waldemar Vollmer ◽

Alexander Tomasz

Keyword(s):

Streptococcus Pneumoniae ◽

Mouse Model ◽

Virulence Factor ◽

Putative Virulence Factor ◽

Capsular Type ◽

Gene Encoding ◽

Type Iii

ABSTRACT Many glucosamine residues of the pneumococcal peptidoglycan (PG) are not acetylated, which makes the PG resistant to lysozyme. A capsular type III mutant with an inactivated pgdA gene (encoding the peptidoglycan N-acetylglucosamine deacetylase A) became hypersensitive to exogenous lysozyme and showed reduced virulence in the intraperitoneal mouse model.

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Ultrastructural characterization of peripheral denervation in a mouse model of Type III spinal muscular atrophy

Journal of Neural Transmission ◽

10.1007/s00702-021-02353-9 ◽

2021 ◽

Author(s):

Federica Fulceri ◽

Francesca Biagioni ◽

Fiona Limanaqi ◽

Carla L. Busceti ◽

Larisa Ryskalin ◽

...

Keyword(s):

Mouse Model ◽

Spinal Muscular Atrophy ◽

Motor Neuron ◽

Motor Neurons ◽

Muscular Atrophy ◽

Disease Onset ◽

Muscle Spindles ◽

Neuromuscular Disorder ◽

Type Iii ◽

Smn Protein

AbstractSpinal muscular atrophy (SMA) is a heritable, autosomal recessive neuromuscular disorder characterized by a loss of the survival of motor neurons (SMN) protein, which leads to degeneration of lower motor neurons, and muscle atrophy. Despite SMA being nosographically classified as a motor neuron disease, recent advances indicate that peripheral alterations at the level of the neuromuscular junction (NMJ), involving the muscle, and axons of the sensory-motor system, occur early, and may even precede motor neuron loss. In the present study, we used a mouse model of slow progressive (type III) SMA, whereby the absence of the mouse SMN protein is compensated by the expression of two human genes (heterozygous SMN1A2G, and SMN2). This leads to late disease onset and prolonged survival, which allows for dissecting slow degenerative steps operating early in SMA pathogenesis. In this purely morphological study carried out at transmission electron microscopy, we extend the examination of motor neurons and proximal axons towards peripheral components, including distal axons, muscle fibers, and also muscle spindles. We document remarkable ultrastructural alterations being consistent with early peripheral denervation in SMA, which may shift the ultimate anatomical target in neuromuscular disease from the spinal cord towards the muscle. This concerns mostly mitochondrial alterations within distal axons and muscle, which are quantified here through ultrastructural morphometry. The present study is expected to provide a deeper knowledge of early pathogenic mechanisms in SMA.

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Eggshell membrane promotes homeostasis of elastic skin and lung tissue associated with type III collagen and decorin expression and ameliorates pulmonary fibrosis in a bleomycin mouse model

10.21203/rs.3.rs-354057/v2 ◽

2021 ◽

Author(s):

Eri Ohto-Fujita ◽

Miho Shimizu ◽

Aya Atomi ◽

Nozomi Hatakeyama ◽

Shinya Horinouchi ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Mouse Model ◽

Mouse Skin ◽

Dermal Fibroblasts ◽

Eggshell Membrane ◽

Lung Fibroblasts ◽

Papillary Dermis ◽

Type Iii Collagen ◽

Double Blind Study ◽

Type Iii

Abstract The skin and lungs are barriers to environmental threats such as toxic chemicals and microbial pathogens. The integrity of the extracellular matrix (ECM) in the dermal papillae in the skin and the interstitium in the lungs is critical for tissue homeostasis. However, it is difficult to improve the ECM integrity in the skin and lung simultaneously. Previously, we reported that eggshell membrane (ESM) provided a young ECM environment to dermal fibroblasts in vitro and in mouse skin and increased the elasticity of human skin. Herein, lung fibroblasts cultured on ESM showed markedly higher type III collagen, decorin, and MMP2 levels. Oral ESM administration in mice markedly increased the type III collagen and decorin levels in lung tissues after 2 weeks, and type III collagen, decorin, and MMP2 levels in the papillary dermis after 4 weeks. Furthermore, in a double-blind study involving 30 adults, the arm skin elasticity significantly increased after 8 weeks of ESM administration. Simultaneously, the Tiffeneau-Pinelli index, which is correlated with lung elasticity, increased also significantly. To further explore the effects of ESM on the lungs, we used a mouse model of bleomycin-induced fibrosis. In these mice, ESM significantly suppressed fibrosis at 2 weeks and increased the type III collagen levels in the bronchioles and decorin levels in the alveoli, which was implicated in the suppression of lung fibrosis. Thus, oral ESM intake may prevent the age-dependent decline of the papillary dermis and pulmonary fibrosis by improving the extracellular environment in skin and lung tissues.

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Defects in mitochondrial localization and ATP synthesis in the mdx mouse model of Duchenne muscular dystrophy are not alleviated by PDE5 inhibition

Human Molecular Genetics ◽

10.1093/hmg/dds415 ◽

2012 ◽

Vol 22 (1) ◽

pp. 153-167 ◽

Cited By ~ 72

Author(s):

J. M. Percival ◽

M. P. Siegel ◽

G. Knowels ◽

D. J. Marcinek

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Mouse Model ◽

Atp Synthesis ◽

Mdx Mouse ◽

Mitochondrial Localization ◽

Pde5 Inhibition

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A Novel Mouse Model of Enteric Vibrio parahaemolyticus Infection Reveals that the Type III Secretion System 2 Effector VopC Plays a Key Role in Tissue Invasion and Gastroenteritis

mBio ◽

10.1128/mbio.02608-19 ◽

2019 ◽

Vol 10 (6) ◽

Cited By ~ 3

Author(s):

Hyungjun Yang ◽

Marcela de Souza Santos ◽

Julia Lee ◽

Hong T. Law ◽

Suneeta Chimalapati ◽

...

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Mouse Model ◽

Intestinal Mucosa ◽

Type Iii Secretion ◽

Vibrio Parahaemolyticus ◽

Intestinal Disease ◽

Intracellular Pathogen ◽

Content Type ◽

Type Iii

ABSTRACT The Gram-negative marine bacterium Vibrio parahaemolyticus is a common cause of infectious gastroenteritis due to the ingestion of contaminated seafood. Most virulent V. parahaemolyticus strains encode two type III secretion systems (T3SS1 and T3SS2); however, the roles they and their translocated effectors play in causing intestinal disease remain unclear. While studies have identified T3SS1 effectors as responsible for killing epithelial cells in culture, the T3SS2 effectors caused massive epithelial cell disruption in a rabbit ileal loop model. Additional models are thus needed to clarify the pathogen-host interactions that drive V. parahaemolyticus-associated gastroenteritis. Germfree mice were infected with a pathogenic clinical isolate of V. parahaemolyticus, RIMD2210633 (RIMD). The pathogen was found to adhere to as well as invade the cecal mucosa, accompanied by severe inflammation and dramatic mucosal damage, including widespread sloughing of infected epithelial cells. Mice infected with a V. parahaemolyticus strain lacking the T3SS1 (POR2) also developed severe pathology, similar to that seen with RIMD. In contrast, the ΔT3SS2 strain (POR3) appeared unable to invade the intestinal mucosa or cause any mucosal pathology. Confirming a role for TS332 effectors, a strain expressing the T3SS2 but lacking VopC (POR2ΔvopC), a T3SS2 effector implicated in epithelial cell invasion in culture, was strongly attenuated in invading the intestinal mucosa and in causing gastroenteritis, although infection with this mutant resulted in more pathology than the ΔT3SS2 strain. We thus present an experimental system that enables further characterization of T3SS effectors as well as the corresponding host inflammatory response involved in the gastroenteritis caused by invasive V. parahaemolyticus. IMPORTANCE Vibrio parahaemolyticus causes severe gastroenteritis following consumption of contaminated seafood. Global warming has allowed this pathogen to spread worldwide, contributing to recent outbreaks. Clinical isolates are known to harbor an array of virulence factors, including T3SS1 and T3SS2; however, the precise role these systems play in intestinal disease remains unclear. There is an urgent need to improve our understanding of how V. parahaemolyticus infects hosts and causes disease. We present a novel mouse model for this facultative intracellular pathogen and observe that the T3SS2 is essential to pathogenicity. Moreover, we show that the T3SS2 effector VopC, previously shown to be a Rac and Cdc42 deamidase that facilitates bacterial uptake by nonphagocytic cells, also plays a key role in the ability of V. parahaemolyticus to invade the intestinal mucosa and cause gastroenteritis. This experimental model thus provides a valuable tool for future elucidation of virulence mechanisms used by this facultative intracellular pathogen during in vivo infection.

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