PMID- 15919591
OWN - NLM
STAT- MEDLINE
DCOM- 20050922
LR  - 20071114
IS  - 0531-5565 (Print)
IS  - 0531-5565 (Linking)
VI  - 40
IP  - 5
DP  - 2005 May
TI  - Contribution of de novo point mutations to the overall mutational burden in 
      mitochondrial DNA of adult rats.
PG  - 396-402
AB  - This study analyzed the incidence of point mutations in mitochondrial DNA of 
      brain and muscle tissues from young (6-month) and old (24-month) male F344 rats. 
      Coding sequence mutations in subunit 5 of the NADH dehydrogenase gene were 
      detected after high-fidelity PCR amplification and cloning by denaturing gradient 
      gel electrophoresis (DGGE) assay followed by sequencing of detected mutants. In 
      total, almost a thousand individual clones were analyzed both in brain and muscle 
      samples. On average, mtDNA from brain tissue showed a 66% increase with age in 
      mutation frequencies (2.3+/-1.9 vs. 3.8+/-4.5 x 10(-4) mutations/bp, mean+/-SD), 
      which failed to reach statistical significance (p=0.45). Muscle tissues yielded 
      substantially fewer mutants with average mutant frequencies for both young and 
      old rats almost 10 times lower than the corresponding values in the brain tissue 
      (0.3+/-0.4 and 0.5+/-0.6 x 10(-4), respectively). The difference in mutation 
      accumulation between muscle and brain was highly significant in both the younger 
      group (Chi-squared=9.7, p < or = 0.01) and in older animals (Chi-squared=10.9, p 
      < or = 0.001). Molecular analysis of the mutated sequences revealed that almost 
      half were identical sequences recurring in different samples and tissues. Our 
      findings indicate that the process of mutation accumulation in mitochondria 
      begins in the germ-line and/or during earlier stages of life, contributing up to 
      half of the total mutational burden, whereas de novo spontaneous formation of 
      point mutations in adulthood is far less than was anticipated.
FAU - Khaidakov, M
AU  - Khaidakov M
AD  - Department of Geriatrics, University of Arkansas for Medical Sciences, John 
      McClellan VA Hospital, 4300 West 7th Street, Little Rock, AR 72205, USA. 
      khaidakovmagomed@uams.edu
FAU - Chavannes-Turesky, N
AU  - Chavannes-Turesky N
FAU - Cooney, C A
AU  - Cooney CA
FAU - Dupont-Versteegden, E E
AU  - Dupont-Versteegden EE
FAU - Kennedy, R H
AU  - Kennedy RH
FAU - Siegel, E R
AU  - Siegel ER
FAU - Khaidakova, G
AU  - Khaidakova G
FAU - Shmookler Reis, R J
AU  - Shmookler Reis RJ
LA  - eng
GR  - P01AG20641/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050328
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - 0 (DNA Transposable Elements)
RN  - 0 (DNA, Mitochondrial)
SB  - IM
MH  - Aging/genetics
MH  - Animals
MH  - Cerebral Cortex/physiology
MH  - DNA Mutational Analysis/methods
MH  - DNA Transposable Elements/genetics
MH  - DNA, Mitochondrial/*genetics
MH  - Electrophoresis/methods
MH  - Male
MH  - Muscle, Skeletal/physiology
MH  - Plasmids/genetics
MH  - Point Mutation/*genetics
MH  - Rats
MH  - Rats, Inbred F344
EDAT- 2005/05/28 09:00
MHDA- 2005/09/24 09:00
CRDT- 2005/05/28 09:00
PHST- 2004/11/17 00:00 [received]
PHST- 2005/02/10 00:00 [revised]
PHST- 2005/02/16 00:00 [accepted]
PHST- 2005/05/28 09:00 [pubmed]
PHST- 2005/09/24 09:00 [medline]
PHST- 2005/05/28 09:00 [entrez]
AID - S0531-5565(05)00030-6 [pii]
AID - 10.1016/j.exger.2005.02.007 [doi]
PST - ppublish
SO  - Exp Gerontol. 2005 May;40(5):396-402. doi: 10.1016/j.exger.2005.02.007. Epub 2005 
      Mar 28.