Document Detail


Developmental analysis of the Hba(th-J) mouse mutation: effects on mouse peri-implantation development and identification of two candidate genes.
MedLine Citation:
PMID:  7589805     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Hba(th-J) mouse mutation is a deletion on chromosome 11 that spans the alpha-globin complex and causes alpha-thalassemia in heterozygous animals and in utero death of embryos homozygous for the deletion. We hypothesised that one or more genes closely linked to the Hba locus are also deleted in these mutant mice and that deletion of these additional genes is responsible for the embryo lethality. We have analysed the developmental profile of mutant embryos using a PCR assay to distinguish homozygous embryos from wild-type and heterozygous embryos. No homozygous embryos are detectable on Day 6.5 of gestation and morphological analysis of embryos on Day 5.5 shows that both the embryonic and extraembryonic ectoderm of the egg cylinder are reduced in size and contain degenerate cells. Preimplantation homozygous embryos are morphologically normal with the same proportion developing to the blastocyst stage as control embryos. However, the cell number of homozygous embryos on Day 4.5 is significantly reduced due predominantly to a decrease in the cell number of the trophectoderm and not the inner cell mass. When homozygous blastocysts are plated in vitro, outgrowth of giant trophectoderm cells appears similar to that of wild-type embryos but outgrowth of the inner cell mass is affected. Cells from the inner cell mass of homozygous embryos appear to undergo necrosis and dissociate from the trophectoderm outgrowth after 3 to 4 days in culture. These studies demonstrate that the development of both the inner cell mass and the trophectoderm of embryos homozygous for the Hbath-J deletion is affected by the mutation. We have used quantitative Southern blotting to show that 3-methyladenine glycosylase (mpg) and dist1, two genes closely linked to the Hba locus on chromosome 11, are also deleted in this mutation. Reverse transcriptase-polymerase chain reaction analyses demonstrate that mpg and dist1 are normally expressed by preimplantation and early postimplantation embryos, whereas alpha-globin transcripts from the Hba locus are not detected until Day 7.5 of gestation. These studies demonstrate that deletion of the mpg or dist1 genes is likely to be responsible for the homozygote embryo lethality and the potential roles of these gene products in early embryogenesis are discussed.
Authors:
J Hendrey; D Lin; M Dziadek
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Developmental biology     Volume:  172     ISSN:  0012-1606     ISO Abbreviation:  Dev. Biol.     Publication Date:  1995 Nov 
Date Detail:
Created Date:  1995-12-26     Completed Date:  1995-12-26     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  253-63     Citation Subset:  IM    
Affiliation:
Developmental Biology Laboratory, Monash University, Clayton, Victoria, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Blastocyst / cytology,  pathology*,  physiology*
Chromosome Mapping*
Crosses, Genetic
DNA Primers
Embryonic and Fetal Development*
Female
Fetal Death
Genes, Lethal*
Genotype
Globins / genetics*
Hemoglobin A / genetics*
Heterozygote
Homozygote
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Mutant Strains
Molecular Sequence Data
Polymerase Chain Reaction
RNA / isolation & purification
Sequence Deletion*
Transcription, Genetic
alpha-Thalassemia / genetics*
Chemical
Reg. No./Substance:
0/DNA Primers; 63231-63-0/RNA; 9004-22-2/Globins; 9034-51-9/Hemoglobin A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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