title: Mouse mutants for the nicotinic acetylcholine receptor ß2 subunit display changes in cell adhesion and neurodegeneration response genes.
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.
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, University of California Davis, Davis, California, United States of America.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Rubin
authors.forename: Deborah A
authors.initials: DA
authors.lastname: van der List
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ballesteros
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Goloshchapov
authors.forename: Leo M
authors.initials: LM
authors.lastname: Chalupa
authors.forename: Barbara
authors.initials: B
authors.lastname: Chapman
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015820:Cadherins; D011978:Receptors, Nicotinic