Genetic and Developmental Analysis of X-Inactivation in Interspecific Hybrid Mice Suggests a Role for the Y Chromosome in Placental Dysplasia

Genetic and Developmental Analysis of X-Inactivation in Interspecific Hybrid Mice Suggests a Role for the Y Chromosome in Placental Dysplasia

Myriam Hemberger^a,b, Haymo Kurz^c, Annie Orth^d, Sabine Otto^a, Angela Lüttges^a, Rosemary Elliott^e, Andras Nagy^f, Seong-Seng Tan^g, Patrick Tam^h, Ulrich Zechner^a, and Reinald H. Fundele^a
^a Max-Planck-Institut für Molekulare Genetik, 14195 Berlin, Germany,
^b Health Sciences Centre, University of Calgary, Calgary, Alberta T2N 4N1, Canada,
^c Anatomisches Institut II, 79104 Freiburg, Germany,
^d Laboratoire Génome et Populations, Université de Montpellier, 34095 Montpellier, France,
^e Roswell Park Cancer Institute, Buffalo, New York 14263,
^f Samuel Lunenfeld Research Institute, Toronto M5G 1X5, Canada,
^g Howard Florey Institute, University of Melbourne, Melbourne, Victoria 3010, Australia
^h Children's Medical Research Institute, University of Sydney, Wentworthville, New South Wales 2145, Australia

Corresponding author: Myriam Hemberger, Genes and Development Research Group, University of Calgary, Health Sciences Ctr. Rm. 2153, 3330 Hospital Dr., N.W., Calgary, Alberta T2N 4N1, Canada., mhemberg{at}ucalgary.ca (E-mail)

Communicating editor: P. D. KEIGHTLEY

It has been shown previously that abnormal placental growth,i.e., hyper- and hypoplasia, occurs in crosses and backcrossesbetween different mouse (Mus) species. A locus that contributesto this abnormal development has been mapped to the X chromosome.Unexpectedly, an influence of fetal sex on placental developmenthas been observed, in that placentas attached to male fetusestended to exhibit a more pronounced phenotype than placentasattached to females. Here, we have analyzed this sex dependencein more detail. Our results show that differences between maleand female placental weights are characteristic of interspecificmatings and are not observed in intraspecific Mus musculus matings.The effect is retained in congenic lines that contain differinglengths of M. spretus-derived X chromosome. Expression of theX-linked gene Pgk1 from the maternal allele only and lack ofoverall activity of two paternally inherited X-linked transgenesindicate that reactivation or lack of inactivation of the paternalX chromosome in trophoblasts of interspecific hybrids is nota frequent occurrence. Thus, the difference between male andfemale placentas seems not to be caused by faulty preferentialX-inactivation. Therefore, these data suggest that the sex differenceof placental weights in interspecific hybrids is caused by interactionswith the Y chromosome.

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