Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models.
Fragile X-related disorder
Huntington's disease
Peripheral DNA
Somatic instability
Spinocerebellar ataxia types 1 and 2
Stool
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 05 2022
01 05 2022
Historique:
received:
10
01
2022
accepted:
05
04
2022
pubmed:
12
4
2022
medline:
18
5
2022
entrez:
11
4
2022
Statut:
ppublish
Résumé
Repeat expansion diseases are a large group of human genetic disorders caused by expansion of a specific short tandem repeat tract. Expansion in somatic cells affects age of onset and disease severity in some of these disorders. However, alleles in DNA derived from blood, a commonly used source of DNA, usually show much less expansion than disease-relevant cells in the central nervous system in both humans and mouse models. Here we examined the extent of expansion in different DNA sources from mouse models of the fragile X-related disorders, Huntington's disease, spinocerebellar ataxia type 1 and spinocerebellar ataxia type 2. We found that DNA isolated from stool is a much better indicator of somatic expansion than DNA from blood. As stool is a sensitive and noninvasive source of DNA, it can be useful for studies of factors affecting the risk of expansion, or the monitoring of treatments aimed at reducing expansion in preclinical trials, as it would allow expansions to be examined longitudinally in the same animal and allow significant changes in expansion to be observed much earlier than is possible with other DNA sources.
Identifiants
pubmed: 35403689
pii: 275011
doi: 10.1242/dmm.049453
pmc: PMC9118036
pii:
doi:
Substances chimiques
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests J.B.C. is on the scientific advisory board, and has shares in Triplet Therapeutics, which is a company focused on modulating somatic instability in HD and other diseases. Other authors declare no competing or financial interests.
Références
J Huntingtons Dis. 2018;7(3):259-267
pubmed: 29889076
J Huntingtons Dis. 2021;10(1):149-163
pubmed: 33579860
Ann Neurol. 1997 Apr;41(4):505-11
pubmed: 9124808
J Neural Transm (Vienna). 2009 Dec;116(12):1607-11
pubmed: 19771391
Ann Neurol. 2016 Jun;79(6):983-90
pubmed: 27044000
Nucleic Acids Res. 2021 Nov 18;49(20):11643-11652
pubmed: 34718701
DNA Repair (Amst). 2018 Sep;69:1-5
pubmed: 29990673
Neurobiol Dis. 2019 Dec;132:104559
pubmed: 31376479
Hum Mol Genet. 2009 Aug 15;18(16):3039-47
pubmed: 19465745
Brain. 2019 Jun 19;:
pubmed: 31216018
Brain Sci. 2019 Mar 01;9(3):
pubmed: 30832215
Am J Hum Genet. 2020 Jul 2;107(1):96-110
pubmed: 32589923
Cell. 2015 Jul 30;162(3):516-26
pubmed: 26232222
Front Genet. 2018 Aug 10;9:314
pubmed: 30147707
J Cell Sci. 2011 Apr 15;124(Pt 8):1179-82
pubmed: 21444748
Lab Anim. 2007 Apr;41(2):174-84
pubmed: 17430617
Hum Mol Genet. 2003 Dec 15;12(24):3359-67
pubmed: 14570710
Ann Neurol. 1996 Aug;40(2):199-206
pubmed: 8773601
Hum Mol Genet. 1999 Jan;8(1):115-22
pubmed: 9887339
Expert Opin Emerg Drugs. 2021 Sep;26(3):295-302
pubmed: 34319843
Lab Anim. 2009 Oct;43(4):390-3
pubmed: 19237460
Nat Genet. 1995 Jul;10(3):344-50
pubmed: 7670474
J Neurol. 1999 Sep;246(9):835-9
pubmed: 10525984
Neuromolecular Med. 2020 Mar;22(1):133-138
pubmed: 31587151
Neurobiol Dis. 2011 Oct;44(1):1-8
pubmed: 21624468
FASEB J. 1991 Oct;5(13):2856-9
pubmed: 1655550
J Huntingtons Dis. 2021;10(1):35-51
pubmed: 33579862
Elife. 2021 May 13;10:
pubmed: 33983118
J Mol Diagn. 2016 Sep;18(5):762-774
pubmed: 27528259
Neuron. 2002 Jun 13;34(6):905-19
pubmed: 12086639
Hum Genet. 1995 Mar;95(3):270-4
pubmed: 7868117
Sci Rep. 2020 Oct 26;10(1):18270
pubmed: 33106549
FEBS Lett. 1999 Nov 26;462(1-2):159-60
pubmed: 10580111
Brain Res Bull. 2008 May 15;76(1-2):70-9
pubmed: 18395613
Neuron. 1995 May;14(5):1065-74
pubmed: 7748554
Exp Cell Res. 1958 Jun;14(3):510-31
pubmed: 13562081
J Am Soc Nephrol. 2021 Mar;32(3):614-627
pubmed: 33531352
J Huntingtons Dis. 2021;10(1):123-148
pubmed: 33579861
EBioMedicine. 2019 Oct;48:568-580
pubmed: 31607598
Am J Hum Genet. 1996 Jun;58(6):1212-22
pubmed: 8651298
Hum Genet. 1997 Sep;100(3-4):339-44
pubmed: 9272152
Hum Mol Genet. 2020 Aug 29;29(15):2551-2567
pubmed: 32761094
PLoS Genet. 2018 Oct 12;14(10):e1007719
pubmed: 30312299
Nat Genet. 1994 Apr;6(4):409-14
pubmed: 8054984
Cell. 2019 Aug 8;178(4):887-900.e14
pubmed: 31398342
Hum Mol Genet. 2003 Feb 1;12(3):273-81
pubmed: 12554681
PLoS Genet. 2020 Jun 26;16(6):e1008902
pubmed: 32589669
Proc Natl Acad Sci U S A. 1958 May;44(5):476-83
pubmed: 16590224
Gene. 2007 Jun 15;395(1-2):125-34
pubmed: 17442505
BMC Syst Biol. 2010 Mar 19;4:29
pubmed: 20302627
Hum Mol Genet. 2020 Aug 29;29(15):2496-2507
pubmed: 32601694