Mouse Mutants for the Nicotinic Acetylcholine Receptor ß2 Subunit Display Changes in Cell Adhesion and Neurodegeneration Response Genes

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 May 7

PMID 21547082

Citations 6

Authors

Carol M Rubin

Deborah A van der List

Jose M Ballesteros

Andrey V Goloshchapov

Leo M Chalupa

Barbara Chapman

Affiliations

Soon will be listed here.

Abstract

Mice lacking expression of the ß2 subunit of the neuronal nicotinic acetylcholine receptor (CHRNB2) display abnormal retinal waves and a dispersed projection of retinal ganglion cell (RGC) axons to their dorsal lateral geniculate nuclei (dLGNs). Transcriptomes of LGN tissue from two independently generated Chrnb2-/- mutants and from wildtype mice were obtained at postnatal day 4 (P4), during the normal period of segregation of eye-specific afferents to the LGN. Microarray analysis reveals reduced expression of genes located on the cell membrane or in extracellular space, and of genes active in cell adhesion and calcium signaling. In particular, mRNA for cadherin 1 (Cdh1), a known axon growth regulator, is reduced to nearly undetectable levels in the LGN of P4 mutant mice and Lypd2 mRNA is similarly suppressed. Similar analysis of retinal tissue shows increased expression of crumbs 1 (Crb1) and chemokine (C-C motif) ligand 21 (Ccl21) mRNAs in Chrnb2-/- mutant animals. Mutations in these genes are associated with retinal neuronal degeneration. The retinas of Chrnb2-/- mutants are normal in appearance, but the increased expression of these genes may also be involved in the abnormal projection patterns of RGC to the LGN. These data may provide the tools to distinguish the interplay between neural activity and molecular expression. Finally, comparison of the transcriptomes of the two different Chrnb2-/- mutant strains reveals the effects of genetic background upon gene expression.

Citing Articles

Erdr1 Drives Macrophage Programming via Dynamic Interplay with YAP1 and Mid1.

Wang Y Immunohorizons. 2024; 8(2):198-213.

PMID: 38392560 PMC: 10916360. DOI: 10.4049/immunohorizons.2400004.

Long Non-coding RNAs Gabarapl2 and Chrnb2 Positively Regulate Inflammatory Signaling in a Mouse Model of Dry Eye.

Yang Y, Chen M, Zhai Z, Dai Y, Gu H, Zhou X Front Med (Lausanne). 2021; 8:808940.

PMID: 34957168 PMC: 8703135. DOI: 10.3389/fmed.2021.808940.

Molecular signatures of retinal ganglion cells revealed through single cell profiling.

Laboissonniere L, Goetz J, Martin G, Bi R, Lund T, Ellson L Sci Rep. 2019; 9(1):15778.

PMID: 31673015 PMC: 6823391. DOI: 10.1038/s41598-019-52215-4.

The Mouse Superior Colliculus: An Emerging Model for Studying Circuit Formation and Function.

Ito S, Feldheim D Front Neural Circuits. 2018; 12:10.

PMID: 29487505 PMC: 5816945. DOI: 10.3389/fncir.2018.00010.

Dynamic self-guiding analysis of Alzheimer's disease.

Kurakin A, Bredesen D Oncotarget. 2015; 6(16):14092-122.

PMID: 26041885 PMC: 4546454. DOI: 10.18632/oncotarget.4221.

References

Muir-Robinson G, Hwang B, Feller M . Retinogeniculate axons undergo eye-specific segregation in the absence of eye-specific layers. J Neurosci. 2002; 22(13):5259-64. PMC: 6758243. DOI: 20026563. View

Cang J, Renteria R, Kaneko M, Liu X, Copenhagen D, Stryker M . Development of precise maps in visual cortex requires patterned spontaneous activity in the retina. Neuron. 2005; 48(5):797-809. PMC: 2562716. DOI: 10.1016/j.neuron.2005.09.015. View

Morishita H, Miwa J, Heintz N, Hensch T . Lynx1, a cholinergic brake, limits plasticity in adult visual cortex. Science. 2010; 330(6008):1238-40. PMC: 3387538. DOI: 10.1126/science.1195320. View

Schroeter M, Zickler P, Denhardt D, Hartung H, Jander S . Increased thalamic neurodegeneration following ischaemic cortical stroke in osteopontin-deficient mice. Brain. 2006; 129(Pt 6):1426-37. DOI: 10.1093/brain/awl094. View

Kury P, Zickler P, Stoll G, Hartung H, Jander S . Osteopontin, a macrophage-derived matricellular glycoprotein, inhibits axon outgrowth. FASEB J. 2004; 19(3):398-400. DOI: 10.1096/fj.04-1777fje. View

Li C, Wong W . Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc Natl Acad Sci U S A. 2001; 98(1):31-6. PMC: 14539. DOI: 10.1073/pnas.98.1.31. View

Richard M, Roepman R, Aartsen W, van Rossum A, den Hollander A, Knust E . Towards understanding CRUMBS function in retinal dystrophies. Hum Mol Genet. 2006; 15 Spec No 2:R235-43. DOI: 10.1093/hmg/ddl195. View

Chawla S . Regulation of gene expression by Ca2+ signals in neuronal cells. Eur J Pharmacol. 2002; 447(2-3):131-40. DOI: 10.1016/s0014-2999(02)01837-x. View

den Hollander A, Ghiani M, de Kok Y, Wijnholds J, Ballabio A, Cremers F . Isolation of Crb1, a mouse homologue of Drosophila crumbs, and analysis of its expression pattern in eye and brain. Mech Dev. 2001; 110(1-2):203-7. DOI: 10.1016/s0925-4773(01)00568-8. View

10.

van de Pavert S, Sanz A, Aartsen W, Vos R, Versteeg I, Beck S . Crb1 is a determinant of retinal apical Müller glia cell features. Glia. 2007; 55(14):1486-97. DOI: 10.1002/glia.20561. View

11.

Xu W, Orr-Urtreger A, Nigro F, Gelber S, Sutcliffe C, Armstrong D . Multiorgan autonomic dysfunction in mice lacking the beta2 and the beta4 subunits of neuronal nicotinic acetylcholine receptors. J Neurosci. 1999; 19(21):9298-305. PMC: 6782888. View

12.

Miwa J, Ibanez-Tallon I, Crabtree G, Sanchez R, Sali A, Role L . lynx1, an endogenous toxin-like modulator of nicotinic acetylcholine receptors in the mammalian CNS. Neuron. 1999; 23(1):105-14. DOI: 10.1016/s0896-6273(00)80757-6. View

13.

Feller M . The role of nAChR-mediated spontaneous retinal activity in visual system development. J Neurobiol. 2002; 53(4):556-67. DOI: 10.1002/neu.10140. View

14.

Klomp L, Farhangrazi Z, Dugan L, Gitlin J . Ceruloplasmin gene expression in the murine central nervous system. J Clin Invest. 1996; 98(1):207-15. PMC: 507418. DOI: 10.1172/JCI118768. View

15.

Korostynski M, Kaminska-Chowaniec D, Piechota M, Przewlocki R . Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes. BMC Genomics. 2006; 7:146. PMC: 1553451. DOI: 10.1186/1471-2164-7-146. View

16.

Sandberg R, Yasuda R, Pankratz D, Carter T, Del Rio J, Wodicka L . Regional and strain-specific gene expression mapping in the adult mouse brain. Proc Natl Acad Sci U S A. 2000; 97(20):11038-43. PMC: 27144. DOI: 10.1073/pnas.97.20.11038. View

17.

McLaughlin T, Torborg C, Feller M, OLeary D . Retinotopic map refinement requires spontaneous retinal waves during a brief critical period of development. Neuron. 2003; 40(6):1147-60. DOI: 10.1016/s0896-6273(03)00790-6. View

18.

Iwai L, Kawasaki H . Molecular development of the lateral geniculate nucleus in the absence of retinal waves during the time of retinal axon eye-specific segregation. Neuroscience. 2009; 159(4):1326-37. DOI: 10.1016/j.neuroscience.2009.02.010. View

19.

Stasi K, Nagel D, Yang X, Ren L, Mittag T, Danias J . Ceruloplasmin upregulation in retina of murine and human glaucomatous eyes. Invest Ophthalmol Vis Sci. 2007; 48(2):727-32. DOI: 10.1167/iovs.06-0497. View

20.

Akins M, Benson D, Greer C . Cadherin expression in the developing mouse olfactory system. J Comp Neurol. 2007; 501(4):483-97. DOI: 10.1002/cne.21270. View