Map2k5-Deficient Mice Manifest Phenotypes and Pathological Changes of Dopamine Deficiency in the Central Nervous System

Yumeng Huang; Pei Wang; Rodrigo Morales; Qi Luo; Jianfang Ma

doi:10.3389/fnagi.2021.651638

journal article Open Access Jun 08, 2021

Map2k5-Deficient Mice Manifest Phenotypes and Pathological Changes of Dopamine Deficiency in the Central Nervous System

Yumeng Huang

Pei Wang

Rodrigo Morales Qi Luo

Jianfang Ma

Frontiers in Aging Neuroscience Vol. 13 · Frontiers Media SA

View at Publisher Save 10.3389/fnagi.2021.651638

Abstract

MAP2K5, a member of the MAPK family, is associated with central nervous system disorders. However, neural functional of Map2k5 from animal models were not well examined so far. Here, we established a Map2k5-targeted knockout mouse model to investigate the behavior phenotypes and its underlying molecular mechanism. Our results showed that female Map2k5 mutant mice manifested decreased circadian-dependent ambulatory locomotion, coordination, and fatigue. Male Map2k5 mutant mice displayed impairment in open field exploration and prepulse inhibition of acoustic startle response (ASR) when compared with wild-type controls. Furthermore, Map2k5 mutant mice showed a decreased dopaminergic cell survival and tyrosine hydroxylase levels in nigrostriatal pathway, indicating a crucial role of MAP2K5 in regulating dopamine system in the central nervous system. In conclusion, this is the first study demonstrating that Map2k5 mutant mice displayed phenotypes by disturbing the dopamine system in the central nervous system, implicating Map2k5 mutant mouse as a promising model for many dopamine related disorders.

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References

44

[1]

Accili "A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice." Proc. Natl. Acad. Sci. U.S.A. (1996) 10.1073/pnas.93.5.1945

[2]

Allen "Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria–history, rationale, description, and significance." Sleep Med. (2014) 10.1016/j.sleep.2014.03.025

[3]

Alonso-Navarro "Association between restless legs syndrome and other movement disorders." Neurology (2019) 10.1212/wnl.0000000000007500

[4]

Appari "C1q-TNF-Related Protein-9 promotes cardiac hypertrophy and failure." Circ. Res. (2017) 10.1161/circresaha.116.309398

[5]

Bilel "Pharmacological and behavioral effects of the synthetic cannabinoid AKB48 in Rats." Front. Neurosci. (2019) 10.3389/fnins.2019.01163

[6]

Cabrera-Mendoza "High polygenic burden is associated with blood DNA methylation changes in individuals with suicidal behavior." J. Psychiatr. Res. (2020) 10.1016/j.jpsychires.2020.01.008

[7]

Castro "CDC42 deletion elicits cerebral vascular malformations via increased MEKK3-dependent KLF4 expression." Circ. Res. (2019) 10.1161/circresaha.118.314300

[8]

Cavanaugh "Neuroprotective role of ERK1/2 and ERK5 in a dopaminergic cell line under basal conditions and in response to oxidative stress." J. Neurosci. Res. (2006) 10.1002/jnr.21024

[9]

CRISPOR: intuitive guide selection for CRISPR/Cas9 genome editing experiments and screens

Jean-Paul Concordet, Maximilian Haeussler

Nucleic Acids Research 2018 10.1093/nar/gky354

[10]

Dinev "Extracellular signal regulated kinase 5 (ERK5) is required for the differentiation of muscle cells." EMBO Rep. (2001) 10.1093/embo-reports/kve177

[11]

Ding "Involvement of MEK5/ERK5 signaling pathway in manganese-induced cell injury in dopaminergic MN9D cells." J. Trace Elem. Med. Biol. (2020) 10.1016/j.jtemb.2020.126546

[12]

English "Identification of substrates and regulators of the mitogen-activated protein kinase ERK5 using chimeric protein kinases." J. Biol. Chem. (1998) 10.1074/jbc.273.7.3854

[13]

Frau "Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone." Nat. Neurosci. (2019) 10.1038/s41593-019-0512-2

[14]

Gan-Or "Genetic markers of restless legs syndrome in Parkinson disease." Parkinsonism Relat. Disord. (2015) 10.1016/j.parkreldis.2015.03.010

[15]

Ghani "Novel synthesis of a dual fluorimetric sensor for the simultaneous analysis of levodopa and pyridoxine." Anal. Bioanal. Chem. (2021) 10.1007/s00216-020-03005-9

[16]

Jo "Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target." Genome Res. (2017) 10.1101/gr.211649.116

[17]

Johnson "Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases." Science (2002) 10.1126/science.1072682

[18]

Kang "Haplotype association of the MAP2K5 gene with antipsychotics-induced symptoms of restless legs syndrome among patients with schizophrenia." Psychiatry Investig. (2018) 10.4306/pi.2018.15.1.84

[19]

Kato "Big mitogen-activated kinase regulates multiple members of the MEF2 protein family." J. Biol. Chem. (2000) 10.1074/jbc.m001573200

[20]

Khan "Sensorimotor gating deficits in “two-hit” models of schizophrenia risk factors." Schizophr. Res. (2018) 10.1016/j.schres.2017.10.009

[21]

Pathogenic Upregulation of Glial Lipocalin-2 in the Parkinsonian Dopaminergic System

Byung-Wook Kim, Kyoung Hoon Jeong, Jae-Hong Kim et al.

The Journal of Neuroscience 2016 10.1523/jneurosci.4261-15.2016

[22]

Korner "Brain catecholamine depletion and motor impairment in a Th knock-in mouse with type B tyrosine hydroxylase deficiency." Brain (2015) 10.1093/brain/awv224

[23]

Lalonde "Neuroanatomical pathways underlying the effects of hypothalamo-hypophysial-adrenal hormones on exploratory activity." Rev. Neurosci. (2017) 10.1515/revneuro-2016-0075

[24]

Langley "Mito-Apocynin prevents mitochondrial dysfunction, microglial activation, oxidative damage, and progressive Neurodegeneration in MitoPark transgenic mice." Antioxid Redox Signal. (2017) 10.1089/ars.2016.6905

[25]

Li "Association of BTBD9 and MAP2K5/SKOR1 with restless legs syndrome in Chinese population." Sleep (2017) 10.1093/sleep/zsx028

[26]

Li "Targeted deletion of the ERK5 MAP kinase impairs neuronal differentiation, migration, and survival during adult neurogenesis in the olfactory bulb." PLoS One (2013) 10.1371/journal.pone.0061948

[27]

Liu "Upregulation of MEK5 by Stat3 promotes breast cancer cell invasion and metastasis." Oncol. Rep. (2017) 10.3892/or.2016.5256

[28]

Liu "ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons." Proc. Natl. Acad. Sci. U.S.A. (2003) 10.1073/pnas.1332804100

[29]

Liu "Extracellular signal-regulated kinase (ERK) 5 is necessary and sufficient to specify cortical neuronal fate." Proc. Natl. Acad. Sci. U.S.A. (2006) 10.1073/pnas.0603373103

[30]

Liu "Importance of intervention timing in the effectiveness of antipsychotics." Prog. Neuropsychopharmacol. Biol. Psychiatry (2018) 10.1016/j.pnpbp.2017.02.003

[31]

Moore "Periodic leg movements during sleep are associated with polymorphisms in BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD." Sleep (2014) 10.5665/sleep.4006

[32]

Obara "ERK5 induces ankrd1 for catecholamine biosynthesis and homeostasis in adrenal medullary cells." Cell Signal. (2016) 10.1016/j.cellsig.2015.12.016

[33]

Parmar "ERK1, 2, and 5 expression and activation in dopaminergic brain regions during postnatal development." Int. J. Dev. Neurosci. (2015) 10.1016/j.ijdevneu.2015.06.009

[34]

Pittenger "OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding." J. Affect. Disord. (2016) 10.1016/j.jad.2016.02.021

[35]

Simões "Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation." Cell Death Dis. (2015) 10.1038/cddis.2015.83

[36]

Splinter "Rotigotine: transdermal dopamine agonist treatment of Parkinson’s disease and restless legs syndrome." Ann. Pharmacother. (2007) 10.1345/aph.1h113

[37]

Tapias-Espinosa "Schizophrenia-like reduced sensorimotor gating in intact inbred and outbred rats is associated with decreased medial prefrontal cortex activity and volume." Neuropsychopharmacology (2019) 10.1038/s41386-019-0392-x

[38]

Wang "Targeted deletion of mek5 causes early embryonic death and defects in the extracellular signal-regulated kinase 5/myocyte enhancer factor 2 cell survival pathway." Mol. Cell Biol. (2005) 10.1128/mcb.25.1.336-345.2005

[39]

Winkelmann "Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions." Nat. Genet. (2007) 10.1038/ng2099

[40]

Yang "Association studies of variants in MEIS1, BTBD9, and MAP2K5/SKOR1 with restless legs syndrome in a US population." Sleep Med. (2011) 10.1016/j.sleep.2011.06.006

[41]

Yeomans "Tactile, acoustic and vestibular systems sum to elicit the startle reflex." Neurosci. Biobehav. Rev. (2002) 10.1016/s0149-7634(01)00057-4

[42]

Yun "α-Synuclein accumulation and GBA deficiency due to L444P GBA mutation contributes to MPTP-induced parkinsonism." Mol. Neurodegener. (2018) 10.1186/s13024-017-0233-5

[43]

Zhang "Chronic stress remodels synapses in an amygdala circuit-specific manner." Biol. Psychiatry (2019) 10.1016/j.biopsych.2018.06.019

[44]

Zou "Targeted deletion of ERK5 MAP kinase in the developing nervous system impairs development of GABAergic interneurons in the main olfactory bulb and behavioral discrimination between structurally similar odorants." J. Neurosci. (2012) 10.1523/jneurosci.6260-11.2012

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Details

Published: Jun 08, 2021
Vol/Issue: 13
License: View

Authors

Fred Hutchinson Cancer Research Center , Seattle , USA

Funding

Innovative Research Group Project of the National Natural Science Foundation of China

National Key Research and Development Program of China

Cite This Article

Yumeng Huang, Pei Wang, Rodrigo Morales, et al. (2021). Map2k5-Deficient Mice Manifest Phenotypes and Pathological Changes of Dopamine Deficiency in the Central Nervous System. Frontiers in Aging Neuroscience, 13. https://doi.org/10.3389/fnagi.2021.651638

Map2k5-Deficient Mice Manifest Phenotypes and Pathological Changes of Dopamine Deficiency in the Central Nervous System

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