Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) are frequently used as model rats not only in studies of essential hypertension and stroke, but also in studies of attention deficit hyperactivity disorder (ADHD). Normotensive Wistar-Kyoto rats (WKY) are normally used as controls in these studies. In this study, using these rats, we aimed to identify the genes causing hypertension and stroke, as well as the genes involved in ADHD.

Computational search for over-represented 8-mers within the 5'-regulatory regions of 634 mouse testis-specific genes.

Accumulation of microarray data has enabled the computational analysis of gene expressions in various tissues. Although the genes showing testis-specific expression are most abundant among the genes exhibiting tissue-specific expression, no systematic study has been conducted for over-represented motifs within their regulatory regions. We have identified 117 over-represented 8-mers that appeared 2648 times within the regulatory regions of 634 testis-specific genes.

In silico study of a novel gene evolved from an ancestral SVIP gene and highly expressed in the adult mouse testes.

We found that a cDNA clone isolated from a mouse testis cDNA library, 1700015G11 (Mmu_15G11), corresponded to the most highly expressed testis-specific mRNA in the adult mouse. Although the Mmu_15G11 cDNA is predicted to encode a small protein consisting of 67 amino acid residues, it has not yet been functionally annotated and has been designated as an unclassifiable clone. Since the Mmu_15G11 protein possibly has a pivotal role in spermatogenesis, we initiated an in silico study of this clone, and revealed that an ancestral gene of 15G11 genes evolved from an ancestral gene for mammalian small valosin-containing protein-interacting protein (SVIP) genes by gene duplication.

In silico study of whey-acidic-protein domain containing oral protease inhibitors.

Since whey-acidic-protein domain (WAP) containing protease inhibitors such as SLPI (secretory leukocyte protease inhibitor) and elafin (elastase-specific inhibitor) have antimicrobial activities and are thought to play critical roles in mucosal defenses, we are interested in these protease inhibitors. By accessing the Novartis mouse expression database, we found that the four WAP family members, SLPI, WFDC2, WFDC5, and WFDC12, are highly expressed in the oral organs, such as the trachea, tongue, and salivary glands. Since their WAP domains play pivotal roles in the antimicrobial and/or antiprotease activities and their application in therapeutics are expected to have practical value, we collected 98 WAP homologues and tried to predict their physiological functions by analyzing their amino acid sequence structures.

Evolution of interleukin-18 binding proteins and interleukin-1 receptor, type II proteins.

Interleukin-18 (IL-18) is one of the pivotal cytokines controlling the defense mechanism called inflammation. As a first step to develop proteins for controlling the IL-18 level, we initiated a study of IL-18-binding proteins (IL-18BPs). Twenty-four IL-18BP family members, 11 from vertebrates and 13 from chordopoxviruses, were picked from the NCBI database.

Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells.

The rae28 gene (rae28), also designated as mph1, is a mammalian ortholog of the Drosophila polyhomeotic gene, a member of Polycomb group genes (PcG). rae28 constitutes PcG complex 1 for maintaining transcriptional states which have been once initiated, presumably through modulation of the chromatin structure. Hematopoietic activity was impaired in the fetal liver of rae28-deficient animals (rae28-/-), as demonstrated by progressive reduction of hematopoietic progenitors of multilineages and poor expansion of colony forming units in spleen (CFU-S(12)) during embryonic development.