Neuron-Specific HuR-Deficient Mice Spontaneously Develop Motor Neuron Disease

The Journal of Immunology : Official Journal of the American Association of Immunologists
Kevin SunTomasz Herjan

Abstract

Human Ag R (HuR) is an RNA binding protein in the ELAVL protein family. To study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. They performed significantly worse on the rotarod test compared with littermate control mice, indicating coordination deficiency. Using the grip-strength test, it was also determined that the forelimbs of neuron-specific HuR-deficient mice were much weaker than littermate control mice. Immunostaining of the brain and cervical spinal cord showed that HuR-deficient neurons had increased levels of cleaved caspase-3, a hallmark of cell apoptosis. Caspase-3 cleavage was especially strong in pyramidal neurons and α motor neurons of HuR-deficient mice. Genome-wide microarray and real-time PCR analysis further indicated that HuR deficiency in neurons resulted in altered expression of genes in the brain involved in cell growth, including trichoplein keratin filament-binding protein, Cdkn2c, G-protein signaling modulator 2, immediate early response 2, superoxide dismutase 1, and Bcl2. The additional enrich...Continue Reading

References

Apr 6, 2001·Cellular and Molecular Life Sciences : CMLS·C M Brennan, J A Steitz
Jun 2, 2001·The New England Journal of Medicine·L P Rowland, N A Shneider
May 6, 2006·Biochimica Et Biophysica Acta·Jean-Pierre Julien, Jasna Kriz
Apr 28, 2007·Proceedings of the National Academy of Sciences of the United States of America·Christian S LobsigerDon W Cleveland
Nov 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Isaac M ChiuMichael C Carroll
Dec 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Trent M WoodruffPeter G Noakes
Mar 17, 2009·Journal of Neuroimmunology·Saima HumayunMichael J Strong
Mar 27, 2009·The EMBO Journal·Kotb AbdelmohsenMyriam Gorospe
Jun 22, 2010·Immunology·Sandra AmorPaul van der Valk
Sep 15, 2010·Journal of Neuropathology and Experimental Neurology·Shigeko TakeuchiMakoto Urushitani
Mar 8, 2011·Current Molecular Medicine·P A McCombe, R D Henderson
Aug 9, 2011·Molecular Neurodegeneration·Jodi MeyerowitzAnthony R White
Mar 13, 2012·Brain Research·Colleen M DeweyGang Yu
Jun 16, 2012·Molecular Neurodegeneration·Zuo-Shang Xu
Jun 19, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomasz HerjanXiaoxia Li
Jun 26, 2013·Free Radical Biology & Medicine·Emanuele D'AmicoHiroshi Mitsumoto
May 27, 2014·Experimental Neurology·T Philips, J D Rothstein
May 27, 2014·Frontiers in Cellular Neuroscience·Eveliina PollariRashid Giniatullin
Oct 11, 2014·Cell Death and Differentiation·A SklirisD L Kontoyiannis
Jan 6, 2015·Nature Communications·Todd J CohenVirginia M Y Lee
May 2, 2015·The Journal of Clinical Investigation·Owen M PetersRobert H Brown
Dec 3, 2015·Surgical Neurology International·Sara ZareiAngel Chinea
Nov 11, 2016·Nature·J Paul TaylorDon W Cleveland
Apr 7, 2017·Frontiers in Aging Neuroscience·Dmitry PetrovOlivier Hermine

❮ Previous
Next ❯

Citations

Aug 12, 2020·RNA Biology·Janina EhsesMichael A Kiebler
Dec 24, 2018·Neuropathology and Applied Neurobiology·B BorroniE Buratti
Mar 1, 2019·Wiley Interdisciplinary Reviews. RNA·Clinton C MacDonald
Aug 8, 2018·International Journal of Molecular Sciences·Stylianos RavanidisEpaminondas Doxakis
Apr 11, 2021·Cell Death & Disease·Shanshan LiuWencheng Zhang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

ALS: Phenotypes

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized phenotypically by progressive muscle weakness. Clinical phenotypes of ALS can be classified based on the pattern, level, and area of onset (e.g. bulbar, cervical, lumbar). Here is the latest research investigating phenotypes of ALS.

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.

Genetics & Epigenetics of Aging

Dozens of genes are implicated in lifespan, and epigenetic changes during aging affect cell function. This feed focuses on the genetics and epigenetics of aging.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

ALS: Pathogenic Mechanisms

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating pathogenic mechanisms that underlie this genetically heterogeneous disorder.

Brain Aging

Here is the latest research on intrinsic and extrinsic factors, as well as pathways and mechanisms that underlie aging in the central nervous system.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

ALS & FTD: TDP-43

TAR DNA-binding protein 43 (TDP-43) is a pathological protein identified in sporadic Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Here are the latest discoveries pertaining to TDP-43 and these diseases.

ALS: Stress Granules

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by cytoplasmic protein aggregates within motor neurons. TDP-43 is an ALS-linked protein that is known to regulate splicing and storage of specific mRNAs into stress granules, which have been implicated in formation of ALS protein aggregates. Here is the latest research in this field.

Related Papers

The Journal of Immunology : Official Journal of the American Association of Immunologists
Kevin SunTomasz Herjan
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
A PramatarovaG A Rouleau
Frontiers in Aging Neuroscience
Fan ZhangXinglong Wang
Frontiers in Molecular Neuroscience
Alexandra LissoubaPierre Drapeau
© 2022 Meta ULC. All rights reserved