The rat and mouse amylase gene families were characterized using sequence data from the UCSC genome assembly. We found that the rat genome contains one amylase‐1 and two amylase‐2 genes, lying close to one another on the same chromosome. Detailed analysis revealed at least six additional amylase pseudogenes in the rat genome in the region adjacent to the amylase‐2 genes. In contrast, the mouse has one amylase‐1 gene and five amylase‐2 genes; the latter are tandemly and systematically arranged on the same chromosome and were generated by segmental duplication. Detailed analysis revealed that the mouse has two amylase pseudogenes, located 5′ to the five amylase‐2 segments. Thus, the amylase genes of mouse and rat tend to be amplified; the sequences of some of them are fixed while others have become pseudogenes during evolution. This is the second report of amylase genomic organization in mammals and the first in the rodents.
The human genome carries multiple copies of sequences related to endogenous retroviral genomes that include long terminal repeat (LTR) sequences. We used the LTR of one such viral genome, called HERV-A, as a probe in Southern analysis to examine the distribution profiles of the hybridizing DNA in the genomes of twelve human × rodent hybrid cell lines carrying one or a few human chromosomes, and in the DNA samples prepared from six sorted, individual chromosomes. The HERV-A sequence was found to be widely distributed among different chromosomes and the Southern patterns for chromosomes 5, the X, and the Y, each obtained in duplicate from independently prepared cell lines or sorted chromosomes, were matched. Chromosome-specific Southern profiles can be used to monitor chromosomes in hybrid cells or to characterize chromosome aberrations, such as deletions.
When neural cells were collected from the entire cerebral cortex of developing mouse fetuses (15.5-17.5 days postcoitum) and their nuclei were transferred into enucleated oocytes, 5.5% of the reconstructed oocytes developed into normal offspring. This success rate was the highest among all previous mouse cloning experiments that used somatic cells. Forty-four percent of live embryos at 10.5 days postcoitum were morphologically normal when premature and early-postmitotic neural cells from the ventricular side of the cortex were used. In contrast, the majority (95%) of embryos were morphologically abnormal (including structural abnormalities in the neural tube) when postmitotic-differentiated neurons from the pial side of the cortex were used for cloning. Whereas 4.3% of embryos cloned with ventricular-side cells developed into healthy offspring, only 0.5% of those cloned with differentiated neurons in the pial side did so. These facts seem to suggest that the nuclei of neural cells in advanced stages of differentiation had lost their developmental totipotency. The underlying mechanism for this developmental limitation could be somatic DNA rearrangements in differentiating neural cells.
ICAM‐3 is a DC‐SIGN ligand that is constitutively expressed on resting leukocytes, and is thus an important molecule for the first immune response. But, ICAM‐3 has not been isolated form rodents. Thus, we compare the ICAM gene clusters in human, dog, mouse, and rat. ICAM‐1, ‐4, ‐5 and ‐3 are located close to one another on the same chromosome and show genomic synteny in human and dog. Almost the same ICAM gene clusters were found in rodent genome, but only the ICAM‐3 was not present. A phylogenetic tree plotting the cDNAs of human, dog, mouse, rat, and bovine suggested that ICAM‐3 was made from a duplication of ICAM‐1. Thus, ICAM‐3 arose from ICAM‐1 in the mammalian evolution, but was lost in the rodent's genome. Our study suggests the different immune response in the rodents in comparison with other mammals.
Abstract Introduction Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by various clinical manifestations. Several cytokines interact and play pathological roles in SLE, although the etiopathology is still obscure. In the present study we investigated the network of immune response-related molecules expressed in the peripheral blood of SLE patients, and the effects of cytokine interactions on the regulation of these molecules. Methods Gene expression profiles of peripheral blood from SLE patients and from healthy women were analyzed using DNA microarray analysis. Differentially expressed genes classified into the immune response category were selected and analyzed using bioinformatics tools. Since interactions among TNF, IFNγ, β-estradiol (E2), and IFNα may regulate the expression of interferon-inducible (IFI) genes, stimulating and co-stimulating experiments were carried out on peripheral blood mononuclear cells followed by analysis using quantitative RT-PCR. Results Thirty-eight downregulated genes and 68 upregulated genes were identified in the functional category of immune response. Overexpressed IFI genes were confirmed in SLE patient peripheral bloods. Using network-based analysis on these genes, several networks including cytokines – such as TNF and IFNγ – and E2 were constructed. TNF-regulated genes were dominant in these networks, but in vitro TNF stimulation on peripheral blood mononuclear cells showed no differences in the above gene expressions between SLE and healthy individuals. Co-stimulating with IFNα and one of TNF, IFNγ, or E2 revealed that TNF has repressive effects while IFNγ essentially has synergistic effects on IFI gene expressions in vitro . E2 showed variable effects on IFI gene expressions among three individuals. Conclusions TNF may repress the abnormal regulation by IFNα in SLE while IFNγ may have a synergistic effect. Interactions between IFNα and one of TNF, IFNγ, or E2 appear to be involved in the pathogenesis of SLE.
