Mitochondrial DNA deletions in mice in men: substantia nigra is much less affected in the mouse.
Mitochondrial DNA (mtDNA) deletions have been reported to accumulate to high levels in substantia nigra of older humans, and these mutations are suspected of causing age-related degeneration in this area. We have compared levels of mtDNA deletions in humans and mice and report here that levels of deletions in the mouse are very significantly lower than in humans. While human mtDNA from substantia nigra contained more than 5% of deleted molecules, mouse substantia nigra contained less than 0.5%. These results imply that mtDNA deletions are unlikely to play any significant role in of murine substantia nigra aging and further call for caution in using mouse models in studies of the role of mtDNA deletions in aging and neurodegeneration. On a more general note, these results support the view that critical targets of the various aging processes may differ significantly between distant species.
Guo
Xinhong
X
Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA.
Kudryavtseva
Elena
E
Bodyak
Natalya
N
Nicholas
Alexander
A
Dombrovsky
Igor
I
Yang
Deye
D
Kraytsberg
Yevgenya
Y
Simon
David K
DK
Khrapko
Konstantin
K
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000818:Animals; D016477:Artifacts; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D051379:Mice; D010300:Parkinson Disease / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods / Q000706:statistics & numerical data; D017384:Sequence Deletion; D013045:Species Specificity; D013378:Substantia Nigra / Q000378:metabolism*
D004272:DNA, Mitochondrial
Nat Genet. 2006 May;38(5):515-7
16604074
Hum Mol Genet. 2001 Jan 1;10(1):17-24
11136709
Expert Rev Mol Diagn. 2005 Sep;5(5):809-15
16149882
Diabetes Obes Metab. 2007 Nov;9 Suppl 2:74-80
17919181
Aging Cell. 2006 Jun;5(3):279-82
16842501
Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-9
9012815
Am J Physiol Renal Physiol. 2007 Jun;292(6):F1751-60
17344189
Nat Genet. 2008 Apr;40(4):392-4
18311139
J Gerontol A Biol Sci Med Sci. 2007 Mar;62(3):235-45
17389720
Ann N Y Acad Sci. 2002 Apr;959:434-47
11976216
Methods Mol Biol. 2009;554:315-27
19513683
Neurosci Lett. 2006 Apr 3;396(3):263-8
16377085
Biotechniques. 1999 Sep;27(3):508-11
10489610
Cancer Res. 1998 Jul 1;58(13):2857-62
9661902
Nature. 2004 May 27;429(6990):417-23
15164064
Genomics. 2000 Oct 15;69(2):151-61
11031098
Nat Genet. 2006 May;38(5):518-20
16604072
J Biol Chem. 1990 Mar 15;265(8):4718-21
2307682
Trends Genet. 2009 Feb;25(2):91-8
19110336
Science. 2005 Jul 15;309(5733):481-4
16020738
Am J Hum Genet. 2006 Sep;79(3):469-80
16909385