Proliferation and growth factor expression in abnormally enlarged placentas of mouse interspecific hybrids.
It has been shown previously that abnormal placental growth occurs in crosses and backcrosses between different mouse (Mus) species. In such crosses, late gestation placentas may weigh between 13 and 848 mg compared with a mean placental weight of approximately 100 mg in late gestation M. musculus intraspecific crosses. A locus on the X-chromosome was shown to segregate with placental dysplasia. Thus in the (M. musculus x M. spretus)F1 x M. musculus backcross, placental hyperplasia cosegregates with a M. spretus derived X-chromosome. Here we have investigated whether increased cell proliferation and aberrant expression of two genes that are involved in placental growth control, Igf2 and Esx1, may cause, or contribute to placental hyperplasia. Increased bromodeoxyuridine labeling of nuclei, reflecting enhanced proliferation, was indeed observed in hyperplastic placentas when compared with normal littermate placentas. Also, increased expression of Igf2 was seen in giant cells and spongiotrophoblast. However, when M. musculus x M. spretus F1 females were backcrossed with males that were heterozygous for a targeted mutation of the Igf2 gene, placentas that carried a M. spretus derived X-chromosome and were negative for a functional Igf2 allele exhibited an intermediate placental phenotype. Furthermore, in early developmental stages of placental hyperplasia, we observed a decreased expression of the X-chromosomal Esx1 gene. This finding suggests that abnormal expression of both Igf2 and Esx1 contributes to abnormal placental development in mouse interspecific hybrids. However, Esx1 is not regulated by IGF2.
Zechner
Ulrich
U
Max-Planck-Institut für Molekulare Genetik, Berlin, Germany.
Hemberger
Myriam
M
Constância
Miguel
M
Orth
Annie
A
Dragatsis
Ioannis
I
Lüttges
Angela
A
Hameister
Horst
H
Fundele
Reinald
R
D000818:Animals; D015152:Blotting, Northern; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D003433:Crosses, Genetic; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006133:Growth Substances / Q000096:biosynthesis*; D006579:Heterozygote; D018398:Homeodomain Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D009929:Organ Size; D010641:Phenotype; D010920:Placenta / Q000002:abnormalities / Q000378:metabolism* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014960:X Chromosome
C107475:Esx1 protein, mouse; D006133:Growth Substances; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D007335:Insulin-Like Growth Factor II; D001973:Bromodeoxyuridine