IDENTIFYING NOVEL GENETIC MODIFIERS OF P53 INVOLVED IN EMBRYONIC LETHALITY

IDENTIFYING NOVEL GENETIC MODIFIERS OF P53 INVOLVED IN EMBRYONIC LETHALITY

Bibliographic Details
Main Author: Liang, Min
Language:English
Published: Ohio University / OhioLINK 2006
Subjects:
P53
Modifiers
Emryonic Lethality
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1135635430
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ohiou11356354302021-08-03T05:43:25Z IDENTIFYING NOVEL GENETIC MODIFIERS OF P53 INVOLVED IN EMBRYONIC LETHALITY Liang, Min P53 Modifiers Emryonic Lethality <p>Lacking both alleles of the tumor suppressor gene p53 results in the lethality of a subset of 129 female mice (16%) in early embryogenesis due to exencephaly. In this study we show that novel genetic modifier genes of p53 can exacerbate embryonic abnormalities. Using a mouse model in which CE mice were crossed with the p53-null 129 mice, a subset of p53+/- and -/- male and female embryos died during gestation. Our hypothesis based on the skewed ratio from Mendellian inheritance in the F2 generation is two genetic modifiers of a p53 null allele lead to an increase in embryonic lethality.</p> <p>We have identified a recessive modifier of the p53 (mop1) locus from CE mice on chromosome 11 centromeric to p53, and a dominant modifier of p53 (mop2) locus from 129 mice on chromosome 11 telomeric to p53. Sequencing of candidate genes within these two regions revealed a transverse mutation (321P to 321S) in the Ovca1 gene within the mop2 locus of CE mice. The mutation increased both mRNA and protein levels of Ovca1 in various tissues in CE mice compared to 129 mice. CE primary cells cultured from different tissues proliferated more rapidly than 129 cells. In addition, CE cells were in G1, S, and G2/M phases while 129 cells have a higher percentage in the G1 phase. Transfection of wild-type Ovca1 into CE cells caused a higher G1 phase arrest. OVCA1 protein localized to punctate bodies clustered around the nucleus in CE mice, while in 129 mice OVCA1 was diffused throughout the cell. Immunohistochemical staining showed that p53+/- abnormal embryos have more proliferating cells than normal embryos, but no obvious difference was observed in differentiated neuronal cells and apoptotic cells. p53-/- small embryos have less differentiated neuronal cells and proliferating cells as well as more apoptotic cells than the normal embryos. Normal and abnormal p53+/- F2 embryos both have the Ovca1 mutation.</p> <p>Thus, Ovca1 combined with mop1, genetically modifies embryonic lethality in p53 deficient mice.</p> 2006-04-14 English text Ohio University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1135635430 http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1135635430 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic P53
Modifiers
Emryonic Lethality
spellingShingle P53
Modifiers
Emryonic Lethality
Liang, Min
IDENTIFYING NOVEL GENETIC MODIFIERS OF P53 INVOLVED IN EMBRYONIC LETHALITY
author Liang, Min
author_facet Liang, Min
author_sort Liang, Min
title IDENTIFYING NOVEL GENETIC MODIFIERS OF P53 INVOLVED IN EMBRYONIC LETHALITY
title_short IDENTIFYING NOVEL GENETIC MODIFIERS OF P53 INVOLVED IN EMBRYONIC LETHALITY
title_full IDENTIFYING NOVEL GENETIC MODIFIERS OF P53 INVOLVED IN EMBRYONIC LETHALITY
title_fullStr IDENTIFYING NOVEL GENETIC MODIFIERS OF P53 INVOLVED IN EMBRYONIC LETHALITY
title_full_unstemmed IDENTIFYING NOVEL GENETIC MODIFIERS OF P53 INVOLVED IN EMBRYONIC LETHALITY
title_sort identifying novel genetic modifiers of p53 involved in embryonic lethality
publisher Ohio University / OhioLINK
publishDate 2006
url http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1135635430
work_keys_str_mv AT liangmin identifyingnovelgeneticmodifiersofp53involvedinembryoniclethality
_version_ 1719424164363763712

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