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

Clark L, Wei M, Cattoretti G, Mendelsohn C, Tycko B - BMC Genet. (2002)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Cancer Genetics, Columbia University College of Physicians and Surgeons, New York, NY, USA. lc654@columbia.edu

ABSTRACT

Background: The Tnfrh1 gene (gene symbol Tnfrsf23) is located near one end of a megabase-scale imprinted region on mouse distal chromosome 7, about 350 kb distant from the nearest known imprinting control element. Within 20 kb of Tnfrh1 is a related gene called Tnfrh2 (Tnfrsf22) These duplicated genes encode putative decoy receptors in the tumor necrosis factor (TNF) receptor family. Although other genes in this chromosomal region show conserved synteny with genes on human Chr11p15.5, there are no obvious human orthologues of Tnfrh1 or Tnfrh2.

Results: 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.

Conclusions: 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.

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Expression of Tnfrh1 in adult and fetal mouse tissues.Tnfrh1 mRNA is detected as two alternative transcripts, both of which are present in most tissues. Both transcripts are most abundant in the placenta. The Tnfrh1 partial cDNA used to probe these blots has no detectable sequence identity with Tnfrh2 over the 5'-most 65 nt, but has 91% identity with the Tnfrh2 over the remaining 450 nt. Stripping and rehybridization at high stringency, with a smaller 5' probe with 72% overall sequence identity over 297 nt gave an identical pattern of bands. Ethidium bromide (EtBr) staining of ribosomal RNA is a loading control. The lanes contain 20 micrograms of total RNA; blots were exposed overnight.
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Figure 3: Expression of Tnfrh1 in adult and fetal mouse tissues.Tnfrh1 mRNA is detected as two alternative transcripts, both of which are present in most tissues. Both transcripts are most abundant in the placenta. The Tnfrh1 partial cDNA used to probe these blots has no detectable sequence identity with Tnfrh2 over the 5'-most 65 nt, but has 91% identity with the Tnfrh2 over the remaining 450 nt. Stripping and rehybridization at high stringency, with a smaller 5' probe with 72% overall sequence identity over 297 nt gave an identical pattern of bands. Ethidium bromide (EtBr) staining of ribosomal RNA is a loading control. The lanes contain 20 micrograms of total RNA; blots were exposed overnight.

Mentions: Previously, Engemann et al. described Tnfrh1 as having ubiquitous expression [4]. Consistent with this, northern blotting using Tnfrh1-specific probes matching the relatively divergent 5' end of this gene showed easily detectable Tnfrh1 mRNA transcripts in nearly all adult tissues, as well as in late fetal organs and structures (Fig.3). However, by far the strongest signals were seen in the pregnant uterus and whole placenta (Fig.3). Measurements by PhosphorImaging showed that Tnfrh1 mRNA in whole placenta was 5-fold more abundant than in the non-pregnant uterus, and 10-fold more abundant than in the whole fetus. Two classes of transcripts were present: the smaller transcript, which migrated at 1.7 kb based on other blots with size standards, matches the size predicted from the cDNA sequence. The larger transcript, which migrates at 3.7 kb, must contain additional sequences, but these have not yet been mapped. To evaluate the relative expression of Tnfrh1 and Tnfrh2 in various organs and tissues, we performed reverse transcription polymerase chain reaction (RT-PCR) in multiplex reactions using a shared downstream primer and Tnfrh1- and Tnfrh2-specific upstream primers. This showed that both genes are expressed in most fetal and adult organs and structures, but that the expression in several structures including placenta and muscle is highly skewed in favor of Tnfrh1 (Fig.4).


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

Clark L, Wei M, Cattoretti G, Mendelsohn C, Tycko B - BMC Genet. (2002)

Expression of Tnfrh1 in adult and fetal mouse tissues.Tnfrh1 mRNA is detected as two alternative transcripts, both of which are present in most tissues. Both transcripts are most abundant in the placenta. The Tnfrh1 partial cDNA used to probe these blots has no detectable sequence identity with Tnfrh2 over the 5'-most 65 nt, but has 91% identity with the Tnfrh2 over the remaining 450 nt. Stripping and rehybridization at high stringency, with a smaller 5' probe with 72% overall sequence identity over 297 nt gave an identical pattern of bands. Ethidium bromide (EtBr) staining of ribosomal RNA is a loading control. The lanes contain 20 micrograms of total RNA; blots were exposed overnight.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC117226&req=5

Figure 3: Expression of Tnfrh1 in adult and fetal mouse tissues.Tnfrh1 mRNA is detected as two alternative transcripts, both of which are present in most tissues. Both transcripts are most abundant in the placenta. The Tnfrh1 partial cDNA used to probe these blots has no detectable sequence identity with Tnfrh2 over the 5'-most 65 nt, but has 91% identity with the Tnfrh2 over the remaining 450 nt. Stripping and rehybridization at high stringency, with a smaller 5' probe with 72% overall sequence identity over 297 nt gave an identical pattern of bands. Ethidium bromide (EtBr) staining of ribosomal RNA is a loading control. The lanes contain 20 micrograms of total RNA; blots were exposed overnight.
Mentions: Previously, Engemann et al. described Tnfrh1 as having ubiquitous expression [4]. Consistent with this, northern blotting using Tnfrh1-specific probes matching the relatively divergent 5' end of this gene showed easily detectable Tnfrh1 mRNA transcripts in nearly all adult tissues, as well as in late fetal organs and structures (Fig.3). However, by far the strongest signals were seen in the pregnant uterus and whole placenta (Fig.3). Measurements by PhosphorImaging showed that Tnfrh1 mRNA in whole placenta was 5-fold more abundant than in the non-pregnant uterus, and 10-fold more abundant than in the whole fetus. Two classes of transcripts were present: the smaller transcript, which migrated at 1.7 kb based on other blots with size standards, matches the size predicted from the cDNA sequence. The larger transcript, which migrates at 3.7 kb, must contain additional sequences, but these have not yet been mapped. To evaluate the relative expression of Tnfrh1 and Tnfrh2 in various organs and tissues, we performed reverse transcription polymerase chain reaction (RT-PCR) in multiplex reactions using a shared downstream primer and Tnfrh1- and Tnfrh2-specific upstream primers. This showed that both genes are expressed in most fetal and adult organs and structures, but that the expression in several structures including placenta and muscle is highly skewed in favor of Tnfrh1 (Fig.4).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Cancer Genetics, Columbia University College of Physicians and Surgeons, New York, NY, USA. lc654@columbia.edu

ABSTRACT

Background: The Tnfrh1 gene (gene symbol Tnfrsf23) is located near one end of a megabase-scale imprinted region on mouse distal chromosome 7, about 350 kb distant from the nearest known imprinting control element. Within 20 kb of Tnfrh1 is a related gene called Tnfrh2 (Tnfrsf22) These duplicated genes encode putative decoy receptors in the tumor necrosis factor (TNF) receptor family. Although other genes in this chromosomal region show conserved synteny with genes on human Chr11p15.5, there are no obvious human orthologues of Tnfrh1 or Tnfrh2.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus