TY - CHAP
T1 - HDL2 Mouse
AU - Rudnicki, Dobrila D.
AU - Yang, X. William
AU - Margolis, Russell L.
N1 - Funding Information:
Portions of this work were supported by NINDS/NIH grants (NS061099, P01 NS16375, NS066111, NS057516) and the Hereditary Disease Foundation grants to R.L.M. D.D.R is supported by NINDS/NIH grant NS064318 and the CHDI Foundation Inc. X.W.Y. is supported by NINDS/NIH grants (NS049501 and NS074312), the Hereditary Disease Foundation, the CHDI Foundation, the McKnight Endowment Fund for Neuroscience, and David Weil Fund to the Semel Institute at University of California at Los Angeles.
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2015
Y1 - 2015
N2 - In 2001, Margolis and colleagues described a new autosomal dominant neurodegenerative disease, Huntington disease-like 2 (HDL2), associated with a CAG/CTG repeat expansion in an alternatively spliced exon of junctophilin 3 that encodes junctophilin 3. HDL2 is a genocopy of Huntington disease (HD)-the genetic, clinical, and neuropathological features of the two diseases are similar. Although overwhelming evidence supports the hypothesis that gain-of-toxic function of expanded polyglutamine is central to HD pathogenesis, HDL2 does not appear to be primarily a polyglutamine disease. Instead, evidence from cell, animal, and human postmortem tissue indicates that HDL2 pathogenesis is multifactorial and includes gain- and loss-of-function mechanisms involving transcripts and their protein products, generated from both strands of the HDL2 locus. The similarity between HD and HDL2 suggest that HD pathogenesis may also include multitranscript, bidirectional aspects, and that looking for points of convergence between HD and HDL2 may help us to elucidate the pathogeneses of both disorders.
AB - In 2001, Margolis and colleagues described a new autosomal dominant neurodegenerative disease, Huntington disease-like 2 (HDL2), associated with a CAG/CTG repeat expansion in an alternatively spliced exon of junctophilin 3 that encodes junctophilin 3. HDL2 is a genocopy of Huntington disease (HD)-the genetic, clinical, and neuropathological features of the two diseases are similar. Although overwhelming evidence supports the hypothesis that gain-of-toxic function of expanded polyglutamine is central to HD pathogenesis, HDL2 does not appear to be primarily a polyglutamine disease. Instead, evidence from cell, animal, and human postmortem tissue indicates that HDL2 pathogenesis is multifactorial and includes gain- and loss-of-function mechanisms involving transcripts and their protein products, generated from both strands of the HDL2 locus. The similarity between HD and HDL2 suggest that HD pathogenesis may also include multitranscript, bidirectional aspects, and that looking for points of convergence between HD and HDL2 may help us to elucidate the pathogeneses of both disorders.
KW - Antisense transcripts
KW - Huntington disease
KW - Huntington disease-like 2
KW - Junctophilin 3
KW - Knockout mouse model
KW - Loss of function
KW - Polyglutamine gain-of-function
KW - RNA neurotoxicity
KW - Transgenic BAC mouse model
KW - Trinucleotide repeats
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U2 - 10.1016/B978-0-12-405195-9.00034-2
DO - 10.1016/B978-0-12-405195-9.00034-2
M3 - Chapter
AN - SCOPUS:84943279512
SN - 9780124051959
SP - 573
EP - 582
BT - Movement Disorders
PB - Elsevier Inc.
ER -