The zebrafish as a model organism to study development of the immune system.
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Animals↗
Biomedical subjects
Gary W Litman
Publications and source records attributed to Gary W Litman.
Cloning novel immune-type inhibitory receptors from the rainbow trout, Oncorhynchus mykiss.
Novel immune-type receptor ( NITR) genes that encode two extracellular immunoglobulin domains and cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs) have been described previously in three lineages of bony fish. In the current study, four ITIM-containing NITR cDNAs are identified in the rainbow trout ( Oncorhynchus mykiss), and their expression patterns and genomic complexity are characterized. The ITIM-containing NITR2 gene maps 1.3 cM from an ITIM-containing C-type lectin receptor ( TCL-2) on linkage group XXI. A comprehensive, phylogenetic analysis of NITRs from rainbow trout and three other major lineages of bony fish defines conserved families of NITRs and suggests an ancient lineage of distinct groups of genes. Several probable scenarios that explain the origins of variant forms of NITRs are described.
Amino Acid Sequence↗
Identification of diversified genes that contain immunoglobulin-like variable regions in a protochordate.
The evolutionary origin of adaptive immune receptors is not understood below the phylogenetic level of the jawed vertebrates. We describe here a strategy for the selective cloning of cDNAs encoding secreted or transmembrane proteins that uses a bacterial plasmid (Amptrap) with a defective beta-lactamase gene. This method requires knowledge of only a single target motif that corresponds to as few as three amino acids; it was validated with major histocompatibility complex genes from a cartilaginous fish. Using this approach, we identified families of genes encoding secreted proteins with two diversified immunoglobulin-like variable (V) domains and a chitin-binding domain in amphioxus, a protochordate. Thus, multigenic families encoding diversified V regions exist in a species lacking an adaptive immune response.
Amino Acid Sequence↗
Structure and diversity of T-lymphocyte antigen receptors alpha and gamma in Xenopus.
Short primer PCR directed at conserved regions of amino acid sequence within the T-cell antigen receptor (TCR) and immunoglobulin (Ig) light chain variable ( V) regions was used to amplify putative TCRgamma V region amplicons from stage 45 Xenopus laevis (African clawed frog) mRNA (cDNA). An adult Xenopus spleen cDNA library was screened using the Vgamma and a putative TCRValpha amplicon. Full copy length cDNAs containing the specific PCR-derived Valpha and Vgamma amplicons were recovered at relatively low frequency. Probes complementing the TCRalpha and TCRgamma constant ( C) regions were employed to isolate equivalent numbers of additional TCR alpha and TCR gamma cDNAs in an unbiased (non- V-based) manner. Few Vgamma genes appear to be expressed relative to the highly diverse expression of V alpha genes in equivalent numbers of cDNAs that were analyzed. Two TCRgamma C regions differ at only two positions; whereas two TCRalpha C regions differ at 33 coding positions as well as in their respective 3' untranslated regions, consistent with two independent loci. However, genomic Southern blots revealed considerably higher numbers of hybridizing bands when probed with C gamma than with C alpha. A potential novel mechanism of diversification is suggested by an unusual TCR alpha cDNA in which the V region can be translated in two frames through utilization of two closely linked V genes and an alternative splicing process. This process produces a translatable cDNA that is not readily predictable from the genomic locus utilizing normal recombination and splicing mechanisms.
Alternative Splicing↗
BIVM, a novel gene widely distributed among deuterostomes, shares a core sequence with an unusual gene in Giardia lamblia.
A novel gene, BIVM (for basic, immunoglobulin-like variable motif-containing), has been identified using an electronic search based on the conservation of short sequence motifs within the variable region of immunoglobulin (Ig) genes. BIVM maps to human chromosome 13q32-q33 and is predicted to encode a 503-amino-acid protein with a pI of 9.1. The 5' untranslated region of BIVM is encoded in two exons; the coding portion is encoded in nine exons. BIVM is tightly linked (41 bp) and in the opposite transcriptional orientation to MGC5302 (also known as KDEL1 and EP58) in human. The ubiquitous expression of BIVM in normal tissues and the presence of a 5' CpG island suggest that BIVM is a housekeeping gene. Characterization of BIVM in representative species demonstrates significant conservation throughout deuterostomes; no sequence with significant identity to BIVM has been detected in proteostomes. However, an unusual gene has been identified in the protozoan pathogen Giardia lamblia that is similar to the core sequence of BIVM, suggesting the possibility of a horizontal gene transfer.
Animals↗
Haplotype exclusion: the unique case presented by multiple immunoglobulin gene loci in cartilaginous fish.
Cartilaginous fish represent the most phylogenetically distant species from man in which immunoglobulin and T cell antigen receptor genes have been identified. Immunoglobulin genes in cartilaginous fish are organized in hundreds of clusters, located on different chromosomes and presumably are under independent regulation; large numbers of immunoglobulin gene clusters are germline-joined and thus their expression is not directly dependent on somatic rearrangement. Despite the unusual nature of immunoglobulin gene genetics in these species, preliminary characterization of the transcription products of immunoglobulin loci in single cell isolates is consistent with haplotype exclusion. Certain features of immunoglobulin gene organization and expression in cartilaginous fish are remarkably similar to that of odorant receptors and suggest that at the level of transcriptional regulation, at least two different mechanisms could exist that relate to haplotype exclusion.
Alleles↗
Zebrafish as an immunological model system.
Two decades of research have established the zebrafish (Danio rerio) as a significant model system for studying vertebrate development and gene structure-function relationships. Recent advances in mutation screening, the creation of genomic resources, including the Zebrafish Genome Project and the development of efficient transgenesis procedures, make this model increasingly attractive for immunological study.
Animals↗