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Biomedical subjects

N Wakasugi

Publications and source records attributed to N Wakasugi.

At least 19 recordsLinked to original sources
PubMed2003

Differences in embryonic development in sensitive and resistant matings to pregnancy block stimuli in mice.

Pregnancy block from exposure to foreign male mouse pheromones is sensitive to both male and female mating strain, as well as the foreign male pheromone-producing strain. Incidence of pregnancy block by male pheromones in mice is different depending on the combination of females, stud males and stimulus males. BALB/cA females mated with BALB/cA males showed a 100% pregnancy block when exposed to males of the DDK strain (Chung et al., 1997). In contrast, BALB/cA females mated with males of dissimilar strain show high rates of pregnancy even if they are exposed to DDK males; this difference is thought to be due to the difference in viability of embryos (Chung et al., 1999). The present study investigated how development of BALB/cA and F1 embryos differ under the influence of pregnancy block stimuli. F1 embryos had significantly higher numbers of cells than did the BALB/cA embryos (P<0.05) at day 3 of pregnancy after exposure to DDK males or after bromocriptine (dopamine agonist, 4 mg kg(-1), i.p.) treatment. Histological observation after bromocriptine treatment revealed that: (i) on day 4 of pregnancy, BALB/cA embryos tended to form a large blastocoel, but showed abnormalities such as degeneration of primitive endoderm and depression of the outer trophoblast-distal endoderm layer at the periphery of the inner cell mass (ICM) or detachment of the ICM from the outer layer. In contrast, 60-70% of F1 embryos were normal late blastocysts and incipient egg cylinders, but 28-40% of early blastocysts were degenerating; and (ii) day 5 BALB/cA embryos were in the range from incipient egg cylinder with a large proamniotic cavity to ectoplacental cone only, but their proximal endoderm and trophoblast-distal endoderm layer were degenerating. In contrast, the F1 embryos were mostly at the egg cylinder stage and maintained normal structure except for occasional enlargement of the developing yolk sac cavity. These results indicate that the lining of the inner surface of trophoblast by distal endoderm layer may be more firmly established and that the inner environment for development of F1 embryos may be more effectively maintained, thereby making them more resistant to deleterious influences due to pregnancy block stimuli than are BALB/cA embryos.

Animals↗
PubMed2000

Modification of survival rate of mouse embryos developing in heterozygous females for ovum mutant gene.

The DDK syndrome (polar infertility) is caused by an incompatibility system due to the ovum mutant (Om) locus. For brevity, the following gene symbols are used in the present report: DDK allele, Om; C57BL/6Cr allele, +. In this investigation, we first attempted to introduce the Om allele of DDK strain into the genetic background of C57BL/6Cr strain. The attempt resulted in the production of no young at the third generation of successive backcrosses. Secondly, mating experiments were performed with heterozygous (Om/+) females having background genes of C57BL/6Cr and DDK strains in the ratios 1:1(B1D), 3:1(B3D), 7:1(B7D), and 15:1(B15D). The survival rate of the embryos as judged by the percentage number of live fetuses/number of corpora lutea at Day 12 of pregnancy was 41.3 +/- 3.2%, 27.3 +/- 3. 2%, 16.4 +/- 3.3%, and 11.3 +/- 3.2% (mean +/- SEM) in the B1D, B3D, B7D, and B15D females, respectively, when they were mated with C57BL/6Cr males. Furthermore, the increased embryonic mortality in the heterozygous (Om/+) females with more background genes of C57BL/6Cr strain was found to be due to a failure in blastocyst formation, as in the DDK syndrome. The parallelism between the proportion of C57BL/6Cr background genes and embryonic mortality has led to a hypothesis proposing the participation of a modifier gene, namely that a mechanism similar to allelic exclusion may be working in the synthesis of cytoplasmic factor of eggs and that only the Om allele is activated during oogenesis to produce DDK-type cytoplasmic factor in heterozygous (Om/+) females having a modifier gene in the homozygous state.

Alleles↗
PubMed1999

Participation of embryonic genotype in the pregnancy block phenomenon in mice.

Pregnancy block by male pheromones in mice differs in incidence depending on the combination of strains. Female mice of BALB/cA strain mated with BALB/cA males show a 100% pregnancy block when exposed to males of inbred strain DDK shortly after copulation (Chung et al., Biol Reprod 1997; 57:312-319). In the present study, BALB/cA females mated with the males of other strains--CBA/J, C3H/HeN, C57BL/6Cr, and IXBL--showed higher pregnancy rates (66.6-87. 5%) even when they were exposed to DDK males. In the pharmacological induction of pregnancy block with dopamine agonist (bromocriptine, 4 mg/kg BW), BALB/cA females mated with BALB/cA males showed a 100% pregnancy block. In contrast, BALB/cA females mated with CBA/J, C3H/HeN, and C57BL/6Cr males showed higher pregnancy rates (40-70%). These results suggest that the better pregnancy rate of BALB/cA females mated with alien males may be due to the stronger viability of F(1) embryos. This interpretation was confirmed by an embryo transfer experiment in which a higher implantation rate was observed when BALB/cA embryos grown in BALB/cA females exposed to BALB/cA males were transferred into recipient BALB/cA females exposed to DDK males. These results suggest that the embryonic genotype or viability of the embryo is one factor contributing to the occurrence of pregnancy block by male pheromones in mice.

Abortion, Veterinary↗
PubMed1997

Embryonic abnormality caused by male pheromonal effect in pregnancy block in mice.

BALB/cA females mated with BALB/cA males and exposed to DDK males showed 100% pregnancy block when exposure started at Days 0-3 of pregnancy. When the exposure to DDK males started at Days 4, 5, 6, and 7, the pregnancy rate was 33.3%, 50%, 90%, and 100%, respectively. (Hereafter, the BALB/cA females exposed to DDK males are referred to as the experimental females, and those exposed to other BALB/cA males as the control females.) Cell number of embryos at Day 3 of pregnancy from the experimental and control females after exposure starting from Day 0 was, respectively, 27.0 +/- 1.2 (mean +/- SEM) vs. 48.6 +/- 1.0 (p < 0.05) for the morulae and 34.8 +/- 1.3 vs. 64.1 +/- 2.0 (p < 0.05) for the blastocysts. Embryos from the experimental and control females after exposure starting from Day 3 or Day 4 were histologically examined after 24-h exposure. Poor development of trophoblast and inner cell mass was observed at Day 4 as general defects of the experimental embryos. In addition, about one third of the embryos were unexpectedly at the more advanced stages than the controls (abnormal overdevelopment). At Day 5, disintegration of the trophoblast layer and primitive endoderm was observed as common abnormalities of experimental embryos, but overdevelopment was not observed at this stage. Disturbance in trophoblast differentiation or failure of its maintenance may be the primary developmental defect displayed by embryos developing in a deteriorated uterine environment under the influence of the odor of alien males.

Animals↗
PubMed1996

Endoplasmic reticulum is missing in dendritic spines of Purkinje cells of the ataxic mutant rat.

Dilute-opisthotonus (dop) is a spontaneous ataxic mutation in the rat, regulated by an autosomal recessive gene. Immunohistochemical staining with anti-inositol 1,4,5-trisphosphate receptor antibody and electron microscopic examinations revealed that the endoplasmic reticulum in dendritic spines of Purkinje cell was missing in the ataxic rat. This could impair the intracellular signal transduction in the parallel fiber-Purkinje cell synapse, and be a cause of the severe ataxic movement.

Animals↗
PubMed1996

Mapping of the dilute-opisthotonus (dop) gene on chromosome 8 of the rat.

The rat dilute-opisthotonus (dop) autosomal recessive gene, causing ataxia and coat color dilution, was mapped on chromosome 8 by PCR-amplified microsatellite markers. To facilitate the linkage analysis, an intersubspecific cross with a Japanese wild rat strain was used. The recombination frequencies were 12.8% between Apoc3 and dop, and 32.1% between dop and Mylc1v. The following order of three genes is proposed; Apoc3-dop-Mylc1v. This mutation appears to be homologous to dilute-lethal (d1) of the mouse in terms of clinical symptoms, coat color effect and chromosomal location of the gene loci. Key words: ataxic mutant rat, dilute-opisthotonus (dop), gene mapping.

Animals↗
PubMed1995

Role of ADF/TRX and its inhibitor on the release of major basic protein from human eosinophils.

Adult T cell leukemia-derived factor (ADF)/Thioredoxin (TRX), originally defined as an IL-2 receptor alpha-chain/p55 inducer, has many cytokine-like activities. We reported that the release of major basic protein (MBP) from mature eosinophils stimulated with cytochalasin B and C5a were augmented after preincubation with recombinant ADF/TRX. The addition of a TRX specific inhibitor, BE40644, suppressed the augmentation of MBP release from mature eosinophils. It is suggested that BE40644 is applicable in allergic diseases associated with eosinophils.

Benzoquinones↗
PubMed1995

A novel partial t haplotype with a brachyury-independent effect on tail phenotype.

The btm (brachyury-interacting tail length modifier) mutation was discovered in strain MOL-NIS derived from Japanese wild mice (Mus musculus molossinus) as an autosomal recessive mutation. Homozygotes for this mutation show a short tail phenotype and, moreover, this mutation causes the tailless character by interacting with the T (brachyury) gene on Chromosome (Chr) 17. Our linkage tests and RFLP analyses suggest that btm is located within the t complex on Chr 17 and represents a new partial t haplotype.

Animals↗
PubMed1995

Long-term influence of sialoadenectomy on reproductive performance of male mice.

The influence of the submandibular gland, the major source of epithelial growth factor, on male reproduction in mice was studied by removing the submandibular gland (sialoadenectomy) and examining its effects on sperm production and copulation and fertility rates over an extended post-operation period. The removal of the submandibular gland caused a decrease in the number of epididymal spermatozoa 4 weeks after the operation; the decrease became significant (P < 0.05) 6-10 weeks after the operation compared with the sham operated and intact groups. There was no significant difference between prepuberal (30 days old) and postpuberal (60 days old) sialoadenectomy, indicating that the submandibular gland is not related to the maturation of the seminiferous tubules. The reduction in the number of epididymal spermatozoa was due to the decrease in number of spermatogonia and spermatocytes per Sertoli cell in the seminiferous tubules. When the reproductive performance was examined over 14 weeks, sialoadenectomized males showed a lower copulation rate and a significantly (P < 0.05) higher incidence of non-fertile copulation compared with the sham-operated and intact males. These results indicate that the submandibular gland and the secretion of epithelial growth factor from it affect spermatogenesis by acting on spermatogonial proliferation and sperm maturation.

Animals↗
PubMed1994

Thioredoxin increases the proliferation of human B-cell lines through a protein kinase C-dependent mechanism.

Thioredoxin (Trx) catalyzes thiol-disulfide oxidoreductions. We and others recently showed that human Trx could function as an autocrine growth factor for human lymphoid cells immortalized by the human T-lymphotrophic virus type I or the Epstein-Barr virus. Here we report that reduced Trx from Escherichia coli generated by NADPH and thioredoxin reductase increases the proliferation of an Epstein-barr virus(+)-B cell line 1G8, which constitutively produces low amounts of human Trx. This proliferative effect involved the activation of protein kinase C through its translocation to the membrane. Staurosporin and calphostin C, two inhibitors of protein kinase C, but not of H8, a protein kinase A inhibitor, were able to block Trx-dependent proliferation. The addition of Trx to 1G8 cells resulted in the formation of inositol 1,4,5-triphosphate and sn-1,2-diacylglycerol by a phosphoinositide-specific phospholipase C, as well as increased free calcium concentration. Diacylglycerol showed a biphasic increase; the first phase, corresponding to an early peak (30 s) of inositol 1,4,5-triphosphate and a second larger, prolonged phase. The second phase was inhibited by propranolol, a specific inhibitor of phosphohydrolase, indicating that it is most likely derived from phosphatidylcholine hydrolysis by the sequential action of phospholipase D and phosphatidic acid phosphohydrolase. Our data suggest that enhanced phosphoinositide-specific phospholipase C activity induced by the dithiol form of Trx in 1G8 cells is associated to protein kinase C activation, and thus plays a role in the permanent growth of Epstein-Barr virus-infected B cells.

B-Lymphocytes↗
PubMed1992

Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62.

A role for redox regulation in activation of the NF-kappa B transcription factor was suggested by the observation that DNA binding activity of free protein, but not preformed DNA-protein complex, is inhibited by -SH modifying agents but enhanced by reducing agents. Mutagenesis of conserved cysteine residues in the p50 subunit identified amino acid 62 as being important for DNA binding, as a serine substitution at this position reduces DNA binding affinity, but renders the protein insensitive to -SH modifying agents. DNA binding activity of the wild type protein but not the amino acid 62 mutant was also stimulated by thioredoxin while detection of disulphide cross linked dimers in p50 but not the amino acid 62 mutant suggests that thioredoxin stimulates DNA binding by reduction of a disulphide bond involving cysteine 62. The physiological relevance of these findings was supported by the observation that cotransfection of a plasmid expressing human thioredoxin and an HIV LTR driven reporter construct resulted in an NF-kappa B dependent increase in expression of the reporter gene. Thus modification of p50 by thioredoxin, a gene induced by stimulation of T-lymphocytes in parallel with NF-kappa B translocation, is a likely step in the cascade of events leading to full NF-kappa B activation.

Amino Acid Sequence↗
PubMed1992

Lymphocyte transformation and thiol compounds; the role of ADF/thioredoxin as an endogenous reducing agent.

ADF (adult T-cell leukemia-derived factor), an inducer of IL-2R with growth promoting activity, is a homologue of thioredoxin which is involved in many thiol-dependent reducing reactions. ADF is constitutively produced and released by human lymphoid cell lines transformed by lymphocyte-tropic viruses, such as human T-lymphotropic virus type I (HTLV-I) and Epstein-Barr virus (EBV). We found that the viability and growth of these ADF high-producer cell lines (ATL-2, HUT102, MT-2, 3B6 and RPM18866) were highly dependent on L-cystine in the culture. In contrast to the relative cystine independency of ADF low-producer cells (Jurkat, Jijoye, U937 and K562), the growth of ADF high-producer cells was almost completely suppressed in L-cystine-free condition. Their viability and growth in L-cystine-free medium were markedly improved by 5 x 10(-5) M L-cysteine, 5 x 10(-5) M 2-ME or 10(-3) M GSH and partially by 10(-3) M DTT. The results demonstrate the requirement of reducing condition involving thiol compounds for the optimal growth of the virally transformed lymphoid cells. Furthermore, recombinant ADF (rADF) and suboptimal dose of 2-ME additively enhanced the growth of ATL-2 cells in L-cystine-free medium, implying the possible involvement of endogenous reducing agents such as ADF/thioredoxin homologue in the process of lymphocyte transformation/activation.

Cell Line↗
PubMed1992

Dotted white--a plumage color mutant in Japanese quail (Coturnix coturnix japonica).

A plumage color mutant, dotted white (DTW), of Japanese quail is described in this paper. The adult DTW mutant shows white plumage with a small colored spot on the head and/or back. The pigmented spots invariably appear on the dorsal region and never on the ventral region of the body. Some birds lack colored spots and show pure white plumage. The chick of the DTW mutant shows cream yellow plumules similar to those of the White Leghorn chick. Colored spots also exist as in adults, and its coloration is diluted light brown. The feathers on colored spots of the adult show diluted pigmentation as compared with wild-type feathers. In addition, the wheat-straw colored shaft streak is extremely narrow and the transversal bars are missing. The DTW mutant is thought to be genetically different from previously reported similar mutants, brown-splashed white, panda, and recessive white. Genetic analyses revealed that the DTW mutant plumage is controlled by an autosomal recessive gene. The gene symbol dtw is provisionally proposed, since there remains a possibility that the DTW character may be allelic to some of the similar mutant characters mentioned above.

Animals↗
PubMed1991

Developmental analysis of the eye lens obsolescence (Elo) gene in the mouse: cell proliferation and Elo gene expression in the aggregation chimera.

This study investigates the primary effect of the eye lens obsolescence (Elo) gene of the mouse. Morphological features of the Elo lens were defined as follows: (1) deficient elongation of lens fiber cells, (2) morphological abnormality of nuclei of lens fiber cells, (3) lack of eosinophilic granules in the central fiber cells and (4) rupture of lens capsule in the posterior region. We have immunohistologically examined, by means of an in vivo BrdU incorporation system, whether or not the Elo gene regulates cell proliferation during lens development. The lens fiber cells were morphologically abnormal in day 13 embryonic Elo lens. However, there were no significant differences in morphology or cell proliferation between normal and Elo lens epithelium until day 14 of gestation. After day 15, the total cell number in the Elo lens epithelium was significantly less than that in the normal, but the total numbers of S-phase cells in the two genotypes were not significantly different. The ratio of the total S-phase cell number to the total number of lens epithelial cells may be affected by the developmental stage, but not directly by the genotype. The genotype, however, may be having a direct influence at later ages because malformation of Elo lens fiber cells must cause reduction of the total number of lens epithelial cells in older embryos. Although, at 30 days old, Elo lens cells were externally extruded through the ruptured capsule into the vitreous cavity, BrdU-labelled lens epithelial cells were detectable. To investigate whether the Elo lens phenotype is determined by its own genotype or by its cellular environment, we produced aggregation chimeras between C3H-Elo/+(C/C) and BALB/c(c/c). Most lenses of BALB/c dominant chimeras were oval in shape without the ruptured lens capsule. However, they were opaque in the center and slightly smaller in size than normal. The lenses of C3H-Elo/+ dominant chimeras were morphologically similar to the Elo lens. Although normal nuclei were regularly arranged in the anterior region, Elo-type nuclei were located in the posterior region. Immunohistological staining by using anti-C3H strain-specific antibody demonstrated that the lens fiber cells with abnormal nuclei were derived only from C3H-Elo/+, not from BALB/c. These observations suggest that the primary effect of the Elo gene in the developing lens may be specific to the fiber cell differentiation rather than to the cell proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

A tail length modifier gene discovered in the Japanese wild mice (Mus musculus molossinus).

The presence of the t haplotypes in strains derived from the Japanese wild mice (Mus musculus molossinus) was investigated. Crosses between the T/+ heterozygous short tailed mice and five normal tailed molossinus strains (MOL-ANJ, MOA, MOL-NEM, MOM and Mns) produced no tailless mice, indicating that these strains possess no t haplotype. In contrast, tailless mice were produced by a cross between the T/+ heterozygotes and a MOL-NIS strain. Mating experiments showed that the tailless character was due to an interaction between the T gene and an autosomal recessive gene carried by the MOL-NIS strain that expresses the short tail character under the homozygous condition. We have tentatively named this gene brachyury-interacting tail length modifier (btm). It remains to be investigated whether the btm gene is located in the t complex region or in the other locus.

Animals↗
PubMed1991

A new mouse strain manifesting high proteinuria and kidney glomerular defect.

A mutant strain of mice manifesting high proteinuria, wasting syndrome, and kidney glomerular defect was established from the F5 offspring of an interstrain cross of CBA/Nga and RFM/Nga mice. Affected mice had high levels of proteinuria after 40 days of age. The body weight of about 22.6% of affected mice decreased rapidly and they died between 3 and 5 months of age. We learned that this abnormality is controlled by two pairs of autosomal recessive genes; the mutant strain of mice is designated FGS/Nga. The mutant strain has been characterized by high proteinuria and renal lesions with focal sclerosis of glomeruli and tubular atrophy with interstitial nephritis in the kidney resembling the human disease. The FGS/Nga mouse strain is a potential animal model for studying kidney glomerular defect in humans.

Animals↗