Creation of X-linked Alport syndrome rat model with Col4a5 deficiency.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 10 2021
21 10 2021
Historique:
received:
18
05
2021
accepted:
12
10
2021
entrez:
22
10
2021
pubmed:
23
10
2021
medline:
29
1
2022
Statut:
epublish
Résumé
Alport syndrome is an inherited chronic human kidney disease, characterized by glomerular basement membrane abnormalities. This disease is caused by mutations in COL4A3, COL4A4, or COL4A5 gene. The knockout mice for Col4α3, Col4α4, and Col4α5 are developed and well characterized for the study of Alport syndrome. However, disease progression and effects of pharmacological therapy depend on the genetic variability. This model was reliable only to mouse. In this study, we created a novel Alport syndrome rat model utilizing the rGONAD technology, which generated rat with a deletion of the Col4α5 gene. Col4α5 deficient rats showed hematuria, proteinuria, high levels of BUN, Cre, and then died at 18 to 28 weeks of age (Hemizygous mutant males). Histological and ultrastructural analyses displayed the abnormalities including parietal cell hyperplasia, mesangial sclerosis, and interstitial fibrosis. Then, we demonstrated that α3/α4/α5 (IV) and α5/α5/α6 (IV) chains of type IV collagen disrupted in Col4α5 deficient rats. Thus, Col4α5 mutant rat is a reliable candidate for the Alport syndrome model for underlying the mechanism of kidney diseases and further identifying potential therapeutic targets for human renal diseases.
Identifiants
pubmed: 34675305
doi: 10.1038/s41598-021-00354-y
pii: 10.1038/s41598-021-00354-y
pmc: PMC8531394
doi:
Substances chimiques
Col4a5 protein, rat
0
Collagen Type IV
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20836Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
Références
Cell. 2013 Aug 1;154(3):691-703
pubmed: 23890820
Kidney Int. 2014 Jun;85(6):1461-8
pubmed: 24522496
Cell Struct Funct. 1995 Apr;20(2):151-6
pubmed: 7641297
J Exp Anal Behav. 1996 Jan;65(1):129-44
pubmed: 8583193
J Cell Biol. 1996 Dec;135(5):1403-13
pubmed: 8947561
Acta Histochem Cytochem. 2006 Jul 1;39(3):89-94
pubmed: 17327928
BMC Biotechnol. 2018 Apr 2;18(1):19
pubmed: 29606116
Sci Rep. 2020 Nov 3;10(1):18891
pubmed: 33144651
J Clin Lab Immunol. 1986 Apr;19(4):193-9
pubmed: 3522918
Kidney Int. 2018 May;93(5):1045-1051
pubmed: 29551517
Dev Growth Differ. 2021 Oct;63(8):439-447
pubmed: 34432885
Biochem Biophys Rep. 2018 Dec 12;17:81-86
pubmed: 30582011
Kidney Int. 2003 Feb;63(2):438-46
pubmed: 12631109
J Cell Sci. 2018 Apr 9;131(7):
pubmed: 29632050
Am J Pathol. 2000 Nov;157(5):1649-59
pubmed: 11073824
J Biol Chem. 2013 Dec 13;288(50):35626-35
pubmed: 24142690
J Hum Genet. 2018 Feb;63(2):115-123
pubmed: 29158599
J Am Soc Nephrol. 2006 Jul;17(7):1962-9
pubmed: 16769745
J Biomed Sci. 2020 Aug 2;27(1):84
pubmed: 32741357
Sci Rep. 2019 Aug 19;9(1):12059
pubmed: 31427681
Nat Protoc. 2019 Aug;14(8):2452-2482
pubmed: 31341289
Genes Dev. 1996 Dec 1;10(23):2981-92
pubmed: 8956999
Sci Rep. 2015 Jun 22;5:11406
pubmed: 26096991
J Am Soc Nephrol. 2010 May;21(5):876-83
pubmed: 20378821
Kidney Int. 2009 Nov;76(9):968-76
pubmed: 19710627
Nat Rev Nephrol. 2013 Mar;9(3):170-8
pubmed: 23165304
Nature. 2006 Feb 16;439(7078):851-5
pubmed: 16482158
Nephrol Dial Transplant. 2007 Apr;22(4):1062-9
pubmed: 17287218
Kidney Int. 2018 Aug;94(2):303-314
pubmed: 29759420
Sci Rep. 2021 Mar 29;11(1):7053
pubmed: 33782421
Methods Mol Biol. 2010;597:1-11
pubmed: 20013222
J Biol Chem. 2014 Nov 7;289(45):31526-33
pubmed: 25253698
Genome Biol. 2018 Feb 26;19(1):25
pubmed: 29482575
Methods Mol Biol. 2019;2018:1-41
pubmed: 31228150
Am J Pathol. 2002 Feb;160(2):721-30
pubmed: 11839593
J Am Soc Nephrol. 2004 Jun;15(6):1466-74
pubmed: 15153557
Sci Rep. 2019 Dec 31;9(1):20398
pubmed: 31892712
Mamm Genome. 2017 Aug;28(7-8):302-314
pubmed: 28752194
J Pathol. 1992 Oct;168(2):221-7
pubmed: 1460540
JCI Insight. 2018 Mar 22;3(6):
pubmed: 29563333
J Am Soc Nephrol. 2005 Apr;16(4):977-85
pubmed: 15716328
J Am Soc Nephrol. 2001 Feb;12(2):252-260
pubmed: 11158215
Dis Model Mech. 2016 Dec 1;9(12):1419-1433
pubmed: 27935823
Biomed Res. 2014;35(5):345-50
pubmed: 25355442
Am J Pathol. 1984 Jul;116(1):175-8
pubmed: 6742105
J Cell Biol. 1995 Sep;130(5):1219-29
pubmed: 7657706
Kidney Int. 1998 Mar;53(3):664-71
pubmed: 9507212
Sci Rep. 2016 Jul 05;6:29450
pubmed: 27377778
Nephrol Dial Transplant. 2009 Mar;24(3):731-4
pubmed: 19110486
Matrix Biol. 2017 Jan;57-58:45-54
pubmed: 27576055
Dis Model Mech. 2016 Oct 1;9(10):1069-1072
pubmed: 27736742
Sci Rep. 2018 Nov 14;8(1):16808
pubmed: 30429498