The Tnfrh1 (Tnfrsf23) gene is weakly imprinted in several organs and expressed at the trophoblast-decidua interface

We analyzed Tnfrh1 for evidence of parental imprinting, and characterized its tissue-specific expression. Tnfrh1 mRNA is detectable in multiple adult and fetal tissues, with highest expression in placenta, where in situ hybridization reveals a distinctive population of Tnfrh1-positive cells in maternal decidua, directly beneath the trophoblast giant cells. In offspring of interspecific mouse crosses, Tnfrh1 shows a consistent parent-of-origin-dependent allelic expression bias, with relative repression, but not silencing, of the paternal allele in several organs including fetal liver and adult spleen.Genes preferentially expressed in the placenta are predicted to evolve rapidly, and Tnfrh1 appears to be an example of this phenomenon. In view of its strong expression in cells at the fetal-maternal boundary, Tnfrh1 warrants further study as a gene that might modulate immune or trophic interactions between the invasive placental trophoblast and the maternal decidua. The preferential expression of Tnfrh1 from the maternal allele indicates weak functional imprinting of this locus in some tissues.A well-studied megabase-scale region of DNA on distal mouse chromosome 7 (Chr7) contains multiple genes subject to parental imprinting. Nearly all genes in this region show conserved synteny with genes on human Chr11p15.5. The extended imprinted region appears to have a bipartite structure in that it contains at least two separate imprinted sub-domains. Each of these subdomains is regulated by a distinct imprinting control element. These correspond to short differentially methylated DNA sequences (DMRs) – one immediately upstream of the H19 gene and another within an intron of the Kcnq1 gene. These two elements control, respectively, the allele-specific expression of the H19/Igf2/Ins2 gene cluster, and the second gene cluster containing Kcnq1, the antisense transcriptKcnq1ot1, p57Kip2/Cdkn1c, Slc22a1l, Ipl/Tssc3 and possibly additional genes [1,2]. There is good evidence assigning