Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis.
Using gene targeting in embryonic stem cells, we have derived mice with a null mutation in a DNA mismatch repair gene homolog, PMS2. We observed microsatellite instability in the male germline, in tail, and in tumor DNA of PMS2-deficient animals. We therefore conclude that PMS2 is involved in DNA mismatch repair in a variety of tissues. PMS2-deficient animals appear prone to sarcomas and lymphomas. PMS2-deficient males are infertile, producing only abnormal spermatozoa. Analysis of axial element and synaptonemal complex formation during prophase of meiosis I indicates abnormalities in chromosome synapsis. These observations suggest links among mismatch repair, genetic recombination, and chromosome synapsis in meiosis.
Baker
S M
SM
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201-3098, USA.
Bronner
C E
CE
Zhang
L
L
Plug
A W
AW
Robatzek
M
M
Warren
G
G
Elliott
E A
EA
Yu
J
J
Ashley
T
T
Arnheim
N
N
Flavell
R A
RA
Liskay
R M
RM
D000251:Adenosine Triphosphatases; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008223:Lymphoma / Q000235:genetics; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D000070976:Mismatch Repair Endonuclease PMS2; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D012509:Sarcoma / Q000235:genetics; D012671:Seminiferous Tubules / Q000473:pathology; D017386:Sequence Homology, Amino Acid; D013090:Spermatocytes / Q000473:pathology / Q000648:ultrastructure; D013094:Spermatozoa / Q000473:pathology
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D011994:Recombinant Proteins; D004247:DNA; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C499533:Pms2 protein, mouse; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes