Morula decompaction (mdn), a preimplantation recessive lethal defect in a transgenic mouse line.
The beta S12 transgenic line carries an insertion of exogenous DNA and a deletion of approximately 2 cM on chromosome 1. Transgenic heterozygotes (beta S12/+) were viable and fertile, but homozygous mice (beta S12/beta S12) could not be produced. To determine the stage at which developmental arrest occurred in homozygotes, embryos derived from intercrosses among heterozygotes or from control crosses were examined at various stages. No homozygotes could be detected at postimplantation stages, suggesting that the mutation affected embryogenesis before implantation. Recovery of embryos at 1.5 or 3.5 days postcoitum, followed by culture in vitro, revealed an abnormal class of embryos which constituted one-fourth of the progeny from intercrosses, and thus appeared to represent the beta S12/beta S12 homozygotes. These embryos cleaved normally to the 8-cell stage and formed compacted morulae, but then decompacted without forming a blastocyst, and ceased dividing at approximately the 16-cell stage. Nearly all blastomeres were viable at the time of decompaction, as demonstrated by trypan blue exclusion, indicating that the loss of compaction is not simply a consequence of cell death. When labeled with a short-term lineage marker and aggregated with normal embryos at the early 8-cell stage, homozygous mutant embryos failed to contribute to the resulting blastocysts, indicating that the defect in the maintenance of compaction is cell autonomous. Based on the mutant phenotype, we conclude that this genetic lesion affects a gene (or genes) required for the maintenance of compaction, and propose that it be named morula decompaction (mdn). The phenotype of mdn/mdn embryos appears to be distinct from those caused by other previously described preimplantation lethal mutations or chromosomal deletions.
Cheng
S S
SS
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Costantini
F
F
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000502:physiology*; D002449:Cell Aggregation; D002470:Cell Survival; D002678:Chimera; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D005804:Genes, Lethal; D005808:Genes, Recessive; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009028:Morula / Q000166:cytology / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology
D005914:Globins