Abstract
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.
| Original language | English (US) |
|---|---|
| Title of host publication | Movement Disorders: Genetics and Models: Second Edition |
| Publisher | Elsevier Inc. |
| Pages | 573-582 |
| Number of pages | 10 |
| ISBN (Print) | 9780124051959 |
| DOIs | |
| State | Published - Oct 29 2014 |
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Keywords
- Antisense transcripts
- Huntington disease
- Huntington disease-like 2
- Junctophilin 3
- Knockout mouse model
- Loss of function
- Polyglutamine gain-of-function
- RNA neurotoxicity
- Transgenic BAC mouse model
- Trinucleotide repeats
ASJC Scopus subject areas
- Medicine(all)
Cite this
HDL2 Mouse. / Rudnicki, Dobrila D.; Yang, X. William; Margolis, Russell Louis.
Movement Disorders: Genetics and Models: Second Edition. Elsevier Inc., 2014. p. 573-582.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - HDL2 Mouse
AU - Rudnicki, Dobrila D.
AU - Yang, X. William
AU - Margolis, Russell Louis
PY - 2014/10/29
Y1 - 2014/10/29
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
UR - http://www.scopus.com/inward/record.url?scp=84943279512&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943279512&partnerID=8YFLogxK
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: Genetics and Models: Second Edition
PB - Elsevier Inc.
ER -