PMID- 7565883
OWN - NLM
STAT- MEDLINE
DCOM- 19951103
LR  - 20190702
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 338
IP  - 1-6
DP  - 1995 Oct
TI  - Aneuploidies and micronuclei in the germ cells of male mice of advanced age.
PG  - 59-76
AB  - The objective of this research was to determine whether the frequencies of 
      chromosomally defective germ cells increased with age in male laboratory mice. 
      Two types of chromosomal abnormalities were characterized: (1) testicular 
      spermatid aneuploidy (TSA) as measured by a new method of multi-color 
      fluorescence in situ hybridization (FISH) with DNA probes specific for mouse 
      chromosomes X, Y and 8, and (2) spermatid micronucleus (SMN) analyses using 
      anti-kinetochore antibodies. B6C3F1 mice (aged 22.5 to 30.5 months, heavier than 
      controls but otherwise in good health) showed significant approximately 2.0 fold 
      increases in the aneuploidy phenotypes X-X-8, Y-Y-8, 8-8-X and 8-8-Y with the 
      greatest effects appearing in animals aged greater than 28 months. No age effect 
      was observed, however, in X-Y-8 hyperhaploidy. Major age-related increases were 
      seen in Y-Y-8 and X-X-8 hyperhaploidies suggesting that advanced paternal age is 
      associated primarily with meiosis II rather than meiosis I disjunction errors. A 
      approximately 5 fold increase was also found in the frequency of micronucleated 
      spermatids in aged mice when compared with young controls. All micronuclei 
      detected in the aged animals lacked kinetochore labeling, suggesting that they 
      either did not contain intact chromosomes or the chromosomes lacked detectable 
      kinetochores. The findings of the TSA and SMN assays are consistent with meiotic 
      or premeiotic effects of advanced age on germ cell chromosomes, but there were 
      differences in the age dependencies of aneuploidy and micronuclei. In summary, 
      advanced paternal age may be a risk factor for chromosomal abnormalities (both 
      aneuploidy and structural abnormalities) in male germ cells.
FAU - Lowe, X
AU  - Lowe X
AD  - Biology and Biotechnology Research Program, Lawrence Livermore National 
      Laboratory, Livermore, CA 94550, USA.
FAU - Collins, B
AU  - Collins B
FAU - Allen, J
AU  - Allen J
FAU - Titenko-Holland, N
AU  - Titenko-Holland N
FAU - Breneman, J
AU  - Breneman J
FAU - van Beek, M
AU  - van Beek M
FAU - Bishop, J
AU  - Bishop J
FAU - Wyrobek, A J
AU  - Wyrobek AJ
LA  - eng
GR  - YO1-ES-10203-00/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (DNA Probes)
SB  - IM
MH  - Aging/*genetics
MH  - *Aneuploidy
MH  - Animals
MH  - Centromere/ultrastructure
MH  - *Chromosome Aberrations
MH  - Chromosomes/*genetics/metabolism
MH  - DNA Probes
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Micronuclei, Chromosome-Defective/*genetics
MH  - Micronucleus Tests
MH  - Paternal Age
MH  - Phenotype
MH  - Sex Chromosomes/genetics
MH  - Spermatids/*ultrastructure
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
AID - 0921-8734(95)00012-U [pii]
AID - 10.1016/0921-8734(95)00012-u [doi]
PST - ppublish
SO  - Mutat Res. 1995 Oct;338(1-6):59-76. doi: 10.1016/0921-8734(95)00012-u.