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Mutations at the mouse Fused locus have pleiotropic developmental effects, including the formation of axial duplications in homozygous embryos. The product of the Fused locus, Axin, displays similarities to RGS (Regulators of G-Protein Signaling) and Dishevelled proteins. Mutant Fused alleles that cause axial duplications disrupt the major mRNA, suggesting that Axin negatively regulates the response to an axis-inducing signal. Injection of Axin mRNA into Xenopus embryos inhibits dorsal axis formation by interfering with signaling through the Wnt pathway. Furthermore, ventral injection of an Axin mRNA lacking the RGS domain induces an ectopic axis, apparently through a dominant-negative mechanism. Thus, Axin is a novel inhibitor of Wnt signaling and regulates an early step in embryonic axis formation in mammals and amphibians.

A human poliovirus receptor (PVR) gene was used to generate transgenic mice that express PVR transcripts and poliovirus binding sites in a wide range of tissues: Intracerebral inoculation of PVR transgenic mice with poliovirus type 1, Mahoney strain, resulted in viral replication in the brain and spinal cord and development of paralytic poliomyelitis. P1/Mahoney did not replicate or cause paralysis in nontransgenic mice. PVR transgenic mice failed to develop clinical disease when inoculated intracerebrally with the live attenuated Sabin type 1 vaccine strain. These results demonstrate that the PVR is the major determinant of poliovirus host range in mice. Transgenic mice expressing human PVR should be useful for studying poliovirus neurovirulence, attenuation, and tissue tropism, and for development and testing of poliovirus vaccine strains.

C57BL/6 mice transgenic for a mu heavy chain gene, the VDJ region of which came from the BALB/c hybridoma 17.2.25, expressed high levels of antibody carrying determinants specific for the transgene (idiotypes). The individual antibodies made by hybridomas from transgenic mice, however, were generally encoded by endogenous genes; in most cases the transgene was present but not expressed. The endogenous, idiotype-positive antibodies had heavy chains that were notable for the high frequencies of JH4 (as in the transgene) and VH segments from the VH81X family (unrelated to the transgene). The expression of endogenous genes mimicking the idiotype of the transgene suggests that a rearranged gene introduced into the germ line can activate powerful cellular regulatory influences.

C57BL6 mice transgenic for a μ heavy chain gene, the VDJ region of which came from the BALBc hybridoma 17.2.25, expressed high levels of antibody carrying determinants specific for the transgene (idiotypes). The individual antibodies made by hybridomas from transgenic mice, however, were generally encoded by endogenous genes; in most cases the transgene was present but not expressed. The endogenous, idiotype-positive antibodies had heavy chains that were notable for the high frequencies of J H 4 (as in the transgene) and V H segments from the V H 81X family (unrelated to the transgene). The expression of endogenous genes mimicking the idiotype of the transgene suggests that a rearranged gene introduced into the germ line can activate powerful cellular regulatory influences.

Transgenic mice containing a microinjected rearranged immunoglobulin (Ig) mu heavy chain gene were examined for the effects on DNA rearrangement of the endogenous Ig genes. Abelson murine leukemia virus (A-MuLV) cell lines were isolated from pre-B cells of transgenic mice and of normal littermates. Microinjected mu gene RNA and a mu heavy chain protein were synthesized in every transgenic A-MuLV cell line. Only 10% of normal mouse A-MuLV transformants synthesized mu protein. A germ-line JH allele was observed in 40% of the transgenic lines, demonstrating that the block to endogenous Ig DNA rearrangement occurred at the first step of heavy chain DNA joining. All alleles were rearranged in normal mouse A-MuLV lines. Germline JH alleles were also detected in 10% of the transgenic hybridomas derived from proliferating B cells. Our results support a model of active prevention of rearrangement by the product of successfully rearranged mu genes.

A functionally rearranged mu heavy chain immunoglobulin (lg) gene was introduced into the germ line of mice. The mu gene encodes a polypeptide which, combined with lambda 1 light chains, shows a specificity for binding the hapten NP. Four transgenic mice harboring 20-140 copies of the foreign mu gene expressed the gene specifically in spleen, lymph node, and thymus at a high level. Purified surface lg-positive B cells, Lyt 2-positive mature T cells, and thymocytes transcribed the foreign mu gene at a similarly high level, suggesting that control of lg gene rearrangement might be the only mechanism that determines the specificity of heavy chain gene expression within the lymphoid cell lineage. No transcription of the foreign mu gene was detected in nonlymphoid tissues with the exception of the heart which expressed the gene at a low level. The transgenic mice had up to 400-fold elevated serum levels of NP binding antibody, which contained a heavy chain with the characteristics of the foreign mu gene. The serum levels of endogenous heavy and light chains in transgenic mice appeared to be the same as in normal mice.