title: Loss of cortical and thalamic neuronal tenascin-C expression in a transgenic mouse expressing exon 1 of the human Huntington disease gene.
abstract: A transgenic mouse containing the first exon of the human Huntington's disease (HD) gene has revealed a variety of behavioral and pathophysiological anomalies reminiscent of certain aspects of human Huntington's disease (HD). The present study has found that expression of the extracellular matrix glycoprotein tenascin-C appears to be unaffected in astroglial cells in wild-type and R6/2 transgenic mice that express the mutant huntingtin protein but that it is conspicuously absent in two neuronal populations within the cerebral cortex and thalamus of the R6/2 mice. Loss of tenascin-C expression begins between the fourth and eighth postnatal weeks, coincidental with the onset of abnormal behavioral phenotype and the appearance of intranuclear inclusion bodies and neuropil aggregates. By 12 weeks, R6/2 mice exhibit a complete absence of tenascin-C neuronal immunolabeling, a disappearance of cRNA probe-positive neurons across discrete cytoarchitectonic regions of the dorsal thalamus (e.g., the ventromedial, parafascicular, lateral posterior, and posterior thalamic groups) and frontal cortex, and an accompanying thalamic astrogliosis. The loss of neuronal tenascin-C expression includes structures that are known to send converging excitatory axonal projections to the caudate-putamen, the structure that is most at risk for neurodegeneration in HD. Altered neuronal expression of tenascin-C in R6/2 mice implicates altered transcriptional activities of the mutant huntingtin protein. The abnormal biochemistry and possibly abnormal activity of thalamostriate and corticostriate projection neurons may also affect abnormal neuronal activities in their primary connectional target, the neostriatum, which is severely compromised in HD.
authors.affiliation: Division of Experimental Animal Research, RIKEN, Tsukuba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kusakabe
authors.forename: L
authors.initials: L
authors.lastname: Mangiarini
authors.forename: E D
authors.initials: ED
authors.lastname: Laywell
authors.forename: G P
authors.initials: GP
authors.lastname: Bates
authors.forename: A
authors.initials: A
authors.lastname: Yoshiki
authors.forename: N
authors.initials: N
authors.lastname: Hiraiwa
authors.forename: J
authors.initials: J
authors.lastname: Inoue
authors.forename: D A
authors.initials: DA
authors.lastname: Steindler
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D004195:Disease Models, Animal; D005091:Exons; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007763:Lac Operon; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D019063:Tenascin / Q000032:analysis / Q000235:genetics*; D013788:Thalamus / Q000166:cytology / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D019063:Tenascin