Molecular Basis for Variable Expression of the MHC Class III Complement Genes, C4 and Slp, among Wild-Derived and Laboratory Mouse Strains

2015 ◽  
pp. 229-234
Author(s):  
Masaru Nonaka
1992 ◽  
Vol 175 (2) ◽  
pp. 471-479 ◽  
Author(s):  
G Garnier ◽  
B Ault ◽  
M Kramer ◽  
H R Colten

Factor B (Bf), an enzyme of the alternative pathway of complement activation, is one of four major histocompatibility complex (MHC) class III genes. To ascertain the genetic mechanism for tissue-specific constitutive and regulated expression of Bf, we sequenced the regulatory regions 5' of the gene from mice of different H-2 MHC haplotypes and assessed trans-acting factors, specific DNA binding nucleoproteins, in liver and kidney. Striking tissue-specific differences in constitutive expression of Bf were demonstrated in mice of H-2f or H-2z haplotypes when compared with H-2d or H-2u (kidney and intestinal Bf in H-2d or H-2u much greater than H-2f or H-2z). These differences correlated with a point nucleotide substitution 3 bp downstream of the upstream Bf initiation site that affects interaction with a DNA binding protein. This and additional cis differences localize the sequence substitutions responsible for previously identified restriction fragment length polymorphisms among inbred mouse strains and also reveal two previously unrecognized polymorphisms generated by SmaI and HinfI digestion. Evidence for differences in trans was found in a comparison of DNA binding nucleoproteins from kidney, but not liver, of B10.PL when compared with B10.M. These data, together with the high degree of sequence homology between human and mouse Bf 5' flanking regions, should prompt a search for polymorphic restriction sites and cis binding elements in the Bf promoter that could serve as markers of human MHC-associated renal pathology and variants in local MHC class III gene expression.


Diabetologia ◽  
1993 ◽  
Vol 36 (8) ◽  
pp. 727-733 ◽  
Author(s):  
T. Lund ◽  
S. Shaikh ◽  
E. Kendall ◽  
R. D. Campbell ◽  
M. Hattori ◽  
...  

1997 ◽  
Vol 3 (S2) ◽  
pp. 317-318
Author(s):  
David A. Sanan ◽  
Dale L. Newland

Build-up of visible atherosclerotic plaque in the arteries is readily quantifiable. The mouse and the rabbit provide useful models for understanding the pathogenesis of atherosclerosis by investigating the effects of genetic and dietary perturbations.Although the wild type mouse does not develop atherosclerosis, atherosclerosis susceptibility genes have been identified in some laboratory mouse strains which do. Furthermore, transgenic technology and gene targeting have produced genetically modified mice that express various apolipoproteins, enzymes and cofactors involved in human lipoprotein metabolism. Gene “knockout” technology allows transgene expression without interference from homologous genes. One notable “knockout” mouse, deficient in apolipoprotein E, develops spontaneous atherosclerosis on a normal chow diet. Transgenic modulations of the atherosclerotic responses of these highly susceptible mice are more pronounced and easily measured. Small, cheap and fast breeding, mice are convenient animal models. But to make mice susceptible to atherosclerosis, their genetic background has to be so drastically altered that the resulting lipoprotein metabolism may not model the human metabolism accurately enough.


10.2741/a653 ◽  
2001 ◽  
Vol 6 (3) ◽  
pp. d914-926 ◽  
Author(s):  
Caroline M Milner

2021 ◽  
Author(s):  
Toyoyuki Takada ◽  
Kentaro Fukuta ◽  
Daiki Usuda ◽  
Tatsuya Kushida ◽  
Shinji Kondo ◽  
...  

AbstractLaboratory mouse strains have mosaic genomes derived from at least three major subspecies that are distributed in Eurasia. Here, we describe genomic variations in ten inbred strains: Mus musculus musculus-derived BLG2/Ms, NJL/Ms, CHD/Ms, SWN/Ms, and KJR/Ms; M. m. domesticus-derived PGN2/Ms and BFM/Ms; M. m. castaneus-derived HMI/Ms; and JF1/Ms and MSM/Ms, which were derived from a hybrid between M. m. musculus and M. m. castaneus. These strains were established by Prof. Moriwaki in the 1980s and are collectively named the “Mishima Battery”. These strains show large phenotypic variations in body size and in many physiological traits. We resequenced the genomes of the Mishima Battery strains and performed a comparative genomic analysis with dbSNP data. More than 81 million nucleotide coordinates were identified as variant sites due to the large genetic distances among the mouse subspecies; 8,062,070 new SNP sites were detected in this study, and these may underlie the large phenotypic diversity observed in the Mishima Battery. The new information was collected in a reconstructed genome database, termed MoG+ that includes new application software and viewers. MoG+ intuitively visualizes nucleotide variants in genes and intergenic regions, and amino acid substitutions across the three mouse subspecies. We report statistical data from the resequencing and comparative genomic analyses and newly collected phenotype data of the Mishima Battery, and provide a brief description of the functions of MoG+, which provides a searchable and unique data resource of the numerous genomic variations across the three mouse subspecies. The data in MoG+ will be invaluable for research into phenotype-genotype links in diverse mouse strains.


2001 ◽  
Vol 12 (4) ◽  
pp. 780-794 ◽  
Author(s):  
Jonathan S. Berg ◽  
Bradford C. Powell ◽  
Richard E. Cheney

The past decade has seen a remarkable explosion in our knowledge of the size and diversity of the myosin superfamily. Since these actin-based motors are candidates to provide the molecular basis for many cellular movements, it is essential that motility researchers be aware of the complete set of myosins in a given organism. The availability of cDNA and/or draft genomic sequences from humans,Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana,Saccharomyces cerevisiae, Schizosaccharomyces pombe, andDictyostelium discoideum has allowed us to tentatively define and compare the sets of myosin genes in these organisms. This analysis has also led to the identification of several putative myosin genes that may be of general interest. In humans, for example, we find a total of 40 known or predicted myosin genes including two new myosins-I, three new class II (conventional) myosins, a second member of the class III/ninaC myosins, a gene similar to the class XV deafness myosin, and a novel myosin sharing at most 33% identity with other members of the superfamily. These myosins are in addition to the recently discovered class XVI myosin with N-terminal ankyrin repeats and two human genes with similarity to the class XVIII PDZ-myosin from mouse. We briefly describe these newly recognized myosins and extend our previous phylogenetic analysis of the myosin superfamily to include a comparison of the complete or nearly complete inventories of myosin genes from several experimentally important organisms.


2019 ◽  
Vol 93 (2-3) ◽  
pp. 122-136 ◽  
Author(s):  
Barbara L. Finlay

The question of how complex human abilities evolved, such as language or face recognition, has been pursued by means of multiple strategies. Highly specialized non-human species have been examined analytically for formal similarities, close phylogenetic relatives have been examined for continuity, and simpler species have been analyzed for the broadest view of functional organization. All these strategies require empirical evidence of what is variable and predictable in both the modeled and the model species. Turning to humans, allometric analyses of the evolution of brain mass and brain components often return the interesting, but disappointing answer that volumetric organization of the human brain is highly predictable seen in its phylogenetic context. Reconciling this insight with unique human behavior, or any species-typical behavior, represents a serious challenge. Allometric analyses of the order and duration of mammalian neural development show that, while basic neural development in humans is allometrically predictable, conforming to adult neural architecture, some life history features deviate, notably that weaning is unusually early. Finally, unusual deviations in the retina and central auditory system in the laboratory mouse, which is widely assumed to be “generic,” as well as severe deviations from expected brain allometry in some mouse strains, underline the need for a deeper understanding of phylogenetic variability even in those systems believed to be best understood.


Sign in / Sign up

Export Citation Format

Share Document