Disease relevance of Acvr2b

• To test this hypothesis, we examined laterality defects in mice carrying mutations in both ActRIIB and inversus viscerum (iv) genes, because iv(-/-) mice display a spectrum of laterality defects, including situs inversus, right isomerism, and left isomerism [1].
• ActRIIB mRNA was also found in brain, spinal cord, and ganglion, but usually appeared earlier in development than the ActRII message [2].
• Retinoic acid induces activin receptor IIB mRNA in F9 embryonal carcinoma cells [3].

High impact information on Acvr2b

• In this study we show that disruption of the type IIB activin receptor (ActRIIB) by gene targeting results in altered expression of multiple Hox genes and abnormal patterning of the vertebrae, similar to but severer than retinoic acid (RA)-induced anterior transformation [4].
• We further show that RA and ActRIIB mutation have synergistic effects on vertebral patterning [4].
• None of the left-right patterning abnormalities and organogenesis defects identified in mice carrying mutations in Nodal or in genes encoding ActRIIA and ActRIIB coreceptors, including heart malformations, pulmonary isomerism, right-sided gut, and spleen hypoplasia, were observed in mice lacking ALK7 [5].
• Activin receptor type IIb (ActRIIb) was previously suggested as the only type II membrane receptor triggering myostatin signaling [6].
• From 6.5- to 9.5-days post coitum (p.c.) activin beta A and beta B subunit expression was restricted to the decidua, while activin receptor type IIB messages were exclusively detected in the embryo [7].

Biological context of Acvr2b

• Mouse Acvr2b gene generates four transcriptional isoforms (Acvr2b(1-4)) via alternative splicing of two sequence domains located at the juxtaposition of the transmembrane domain [8].
• To investigate whether these splicing domains are essential for signal transduction of the Acvr2b receptor in vivo, we have generated a strain of mutant mice (Acvr2b(4/4)) which produce only the Acvr2b(4) isoform, which lacks both splicing domains [8].
• In the absence of its subfamily receptor Acvr2a, however, the development of Acvr2b(4/4) mice was arrested at the gastrulation stage, recapitulating the Acvr2a(-/-); Acvr2b(+/-) mutant phenotype [8].
• We show here that the penetrance and severity of the right isomerism is significantly elevated in nodal(+/-); ActRIIB(-/-) mice, compared with ActRIIB(-/-) mice [1].
• Targeted disruption of the mouse activin receptor type IIB gene (Acvr2b) results in abnormal left-right (LR) axis development among Acvr2b-/- homozygotes [Oh and Li, 1997: Genes Dev 11:1812-1826] [9].

Anatomical context of Acvr2b

• The expression of activin receptor type IIB is particularly strong in embryonic ectoderm apparent at E5.5 and continuing through E8 [10].
• The mRNA of activin receptor-IIB was detected in the ovary, in embryos at the 1-cell and the 8-cell/morula stages, and also in the unfertilized egg, although to a lesser extent, but not in the oviduct or in the 2-cell-stage embryo either in vivo or cultured in vitro [11].
• ActRIIB is the type II receptor expressed most in spermatogonia, whereas Sertoli cells specifically expressed BMPRIIB, in addition to ActRIIB [12].
• To investigate whether their function is required for mesoderm formation and gastrulation as implicated in Xenopus studies, we generated mice carrying both receptor mutations by interbreeding the ActRIIA and ActRIIB knockout mutants [13].
• The levels of expression of ActRIIB gene in rat testis or ovary were not changed during development [14].

Associations of Acvr2b with chemical compounds

• Type II activin receptors (ActRII and ActRIIB) are single-transmembrane domain serine/threonine kinase receptors that bind activin to initiate the signaling and cellular responses triggered by this hormone [15].
• Both cycloheximide and actinomycin D inhibited the inductive effect of t-RA on ActR-IIB gene expression, in contrast to ActR-II whose gene expression was not suppressed by cycloheximide but abolished by actinomycin D [3].
• A ligand-receptor pair, bone morphogenetic protein-7 (BMP7) and activin receptor IIB (actRIIB), was identified from a pool of DNA fragments recovered from MCF7 cells treated with 17beta-estradiol (E2) by chromatin immunoprecipitation with antiestrogen receptor-alphaantibody [16].

Other interactions of Acvr2b

• RESULTS.: Transgenic mdx mice carrying the dnActRIIB gene have bigger muscles than mdx mice with the normal gene of ActRIIB [17].
• Follistatin message was observed in all tissues (except the heart and vessels) localizing beta A-subunit and/or ActRIIB but not in the same cell type [2].

Analytical, diagnostic and therapeutic context of Acvr2b

• Northern blot analyses of total RNA from testes of double mutants did not reveal transcriptional up-regulation of activin receptor IIB, the other activin type II receptor [18].
• We have studied the distribution of activin receptor gene expression in the brain, pituitary, ovary, and testis of the adult rat by in situ hybridization, using probes complementary to the mRNAs encoding the mouse activin receptor subtypes II and IIB (ActRII and ActRIIB) [19].

References