Visualization of mosaicism in tissues of normal and mismatch-repair-deficient mice carrying a microsatellite-containing transgene

To determine the frequency of mutation in different cell types of mammals, transgenic mice that allow mutant cells to be visualized in situ were used. These mice carry a defective allele of the human placental alkaline phosphatase (PLAP) gene. The allele does not produce enzyme because the reading f...

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Published inMutation research Vol. 505; no. 1-2; p. 51
Main Authors Hersh, Megan N, Stambrook, Peter J, Stringer, James R
Format Journal Article
LanguageEnglish
Published Netherlands 29.08.2002
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Abstract To determine the frequency of mutation in different cell types of mammals, transgenic mice that allow mutant cells to be visualized in situ were used. These mice carry a defective allele of the human placental alkaline phosphatase (PLAP) gene. The allele does not produce enzyme because the reading frame is shifted by an insertion of 7 G:C basepairs. The insertion is adjacent to four existing G:C basepairs, so the allele has a tract of 11Gs. The G11 PLAP allele was studied in wildtype mice and in mice deficient in mismatch-repair (MMR) due to lack of either Pms2 or Mlh1. PLAP(+) cells were counted in brain, heart, kidney, and liver. In wildtype mice, there was an average of between 5 and 30 PLAP(+) events per million cells. No cells with alkaline phosphatase activity were detected in tissues from mice lacking the PLAP gene. In MMR-deficient mice, the number of PLAP(+) allele was increased by at least three-order of magnitude in brain, heart and kidney, but <10-fold in liver. These data show that MMR is vital to maintaining repeat stability in brain, heart and kidney cells. The reason for the different results in the liver is not clear. Cells in the liver were shown to be capable of expressing of PLAP enzyme and PLAP mRNA was present in this organ.
AbstractList To determine the frequency of mutation in different cell types of mammals, transgenic mice that allow mutant cells to be visualized in situ were used. These mice carry a defective allele of the human placental alkaline phosphatase (PLAP) gene. The allele does not produce enzyme because the reading frame is shifted by an insertion of 7 G:C basepairs. The insertion is adjacent to four existing G:C basepairs, so the allele has a tract of 11Gs. The G11 PLAP allele was studied in wildtype mice and in mice deficient in mismatch-repair (MMR) due to lack of either Pms2 or Mlh1. PLAP(+) cells were counted in brain, heart, kidney, and liver. In wildtype mice, there was an average of between 5 and 30 PLAP(+) events per million cells. No cells with alkaline phosphatase activity were detected in tissues from mice lacking the PLAP gene. In MMR-deficient mice, the number of PLAP(+) allele was increased by at least three-order of magnitude in brain, heart and kidney, but <10-fold in liver. These data show that MMR is vital to maintaining repeat stability in brain, heart and kidney cells. The reason for the different results in the liver is not clear. Cells in the liver were shown to be capable of expressing of PLAP enzyme and PLAP mRNA was present in this organ.
Author Stringer, James R
Hersh, Megan N
Stambrook, Peter J
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/12175905$$D View this record in MEDLINE/PubMed
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CitedBy_id crossref_primary_10_1016_j_mrgentox_2005_09_003
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crossref_primary_10_1073_pnas_0401340102
crossref_primary_10_1016_j_mrfmmm_2004_07_010
crossref_primary_10_1038_nmeth_1182
crossref_primary_10_1038_srep43915
crossref_primary_10_1016_j_mrfmmm_2004_06_036
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Snippet To determine the frequency of mutation in different cell types of mammals, transgenic mice that allow mutant cells to be visualized in situ were used. These...
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StartPage 51
SubjectTerms Adaptor Proteins, Signal Transducing
Adenosine Triphosphatases - deficiency
Adenosine Triphosphatases - physiology
Alkaline Phosphatase
Alleles
Animals
Base Pair Mismatch - genetics
Carrier Proteins
DNA Repair - genetics
DNA Repair Enzymes
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - physiology
Female
Fluorescent Dyes
GPI-Linked Proteins
Humans
Indoles
Isoenzymes - genetics
Liver - enzymology
Male
Mice
Mice, Knockout
Mice, Transgenic - genetics
Microsatellite Repeats - genetics
Microscopy, Fluorescence
Mismatch Repair Endonuclease PMS2
Mosaicism
Mutagenesis, Insertional
Mutation
MutL Protein Homolog 1
Neoplasm Proteins - deficiency
Neoplasm Proteins - physiology
Nitroblue Tetrazolium
Nuclear Proteins
Organ Specificity
Organic Chemicals
Organophosphorus Compounds
Quinazolines
Quinazolinones
RNA, Messenger - analysis
Staining and Labeling
Transgenes - genetics
Title Visualization of mosaicism in tissues of normal and mismatch-repair-deficient mice carrying a microsatellite-containing transgene
URI https://www.ncbi.nlm.nih.gov/pubmed/12175905
Volume 505
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