Biomedical subjects

Liunan Li

Publications and source records attributed to Liunan Li.

4 recordsLinked to original sources

PubMed2006

Gene expression profiling in embryonic mouse lenses.

PURPOSE: In this study, we used laser capture microdissection (LCM) and microarray hybridization technology to compare the gene expression profiles of mouse embryonic days 10 and 12 lenses (E10 and E12). METHODS: Lens cells of C57/BL6 mouse embryos at E10 and E12 were harvested using the PixCell II LCM System. Total RNA was extracted, amplified, labeled, and hybridized to the 430 2.0 mouse chip (Affymetrix) according to the manufacturer's instructions. Data extracted from the images were analyzed using different software programs. Regulated expression of selected genes was confirmed by real-time PCR (RT-PCR). RESULTS: Analysis of the microarray data from E10 and E12 lenses identified 1,573 genes that showed a two fold or greater change in expression level. Among these 1,573 genes, 956 genes were downregulated and 617 were upregulated in E12 lenses. In addition to the upregulated expression of beta- and gamma-crystallin genes, genes that regulate the cell cycle showed significant changes of gene expression during the E10 (lens pit) to E12 (primary fiber cell induction) time period. Genes involved in insulin-like growth factor (IGF) signaling and Wnt (a family of secreted glycoproteins related to the Drosophila segment polarity gene, wingless, and to the proto-oncogene, int-1) signaling were also differentially regulated. In particular, positive regulators of Wnt signaling were downregulated and negative regulators were upregulated, indicating that modulation of Wnt signaling is important for normal lens morphogenesis. CONCLUSIONS: Our results provide new information about differential regulation of gene expression during early lens development. Analysis of global gene expression profiles in embryonic mouse lenses has allowed us to identify several molecular pathways that are differentially regulated during early lens development.

Animals↗

PubMed2006

Regulation of B cell tolerance by the lupus susceptibility gene Ly108.

The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1z/Sle1bz, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1z/Sle1bz impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1bz, among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6.Sle1z mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.

Animals↗

PubMed2004

Pathogenic profiles and molecular signatures of antinuclear autoantibodies rescued from NZM2410 lupus mice.

Two outstanding questions concerning antinuclear antibodies (ANAs) in lupus involve their pathogenic potential and their molecular signatures. To address these questions, a panel of 56 antinuclear and 47 nonnuclear binding monoclonal antibodies was rescued from four seropositive NZM2410 lupus mice. The monoclonals varied in their reactivity to nucleosomes, ssDNA, dsDNA, and glomerular substrate. A large fraction of the antibodies demonstrated apparent polyreactivity (to DNA, histones, and glomerular antigens) due to bound, DNase-1 sensitive nuclear antigenic bridges. Although nephrophilic immunoglobulin (Ig) M and IgG antibodies were the most pathogenic, the dsDNA-binding antibodies were modestly so; in contrast, antinucleosome antibodies were clearly not pathogenic. Compared with the nonnuclear antigen-binding monoclonal antibodies rescued from the same mice, ANAs exhibited increased utilization of VH5/7183 genes and highly cationic heavy chain (HC) CDR3 regions. Most intriguingly, the CDR3 regions of the ANAs exhibited alternating arginine/lysine peaks at H96, H98, and H100, with neutral troughs at H95, H97, and H99. To summarize, glomerular-binding anti-dsDNA antibodies appear to be the most pathogenic variety of lupus autoantibodies. The presence of an alternating charge pattern in their HC CDR3 regions appears to be a prominent hallmark of ANAs.

Amino Acid Sequence↗

PubMed2003

Activins are critical modulators of growth and survival.

Activins betaA and betaB (encoded by Inhba and Inhbb genes, respectively) are related members of the TGF-beta superfamily. Previously, we generated mice with an Inhba knock-in allele (InhbaBK) that directs the expression of activin betaB protein in the spatiotemporal pattern of activin betaA. These mice were small and had shortened life spans, both influenced by the dose of the hypomorphic InhbaBK allele. To understand the mechanism(s) underlying these abnormalities, we now examine growth plates, liver, and kidney and analyze IGF-I, GH, and major urinary proteins. Our studies show that activins modulate the biological effects of IGF-I without substantial effects on GH, and that activin signaling deficiency also has modest effects on hepatic and renal function. To assess the relative influences of activin betaA and activin betaB, we produced mice that express activin betaB from the InhbaBK allele, and not from its endogenous Inhbb locus. InhbaBK/BK, Inhbb-/- mice have failure of eyelid fusion at birth and demonstrate more severe effects on somatic growth and survival than either of the corresponding single homozygous mutants, showing that somatic growth and life span are supported by both activins betaA and betaB, although activin betaA plays a more substantial role.

Animals↗