Biomedical subjects

T Kasugai

Publications and source records attributed to T Kasugai.

At least 55 records · Page 3Linked to original sources

PubMed1995

Pyruvate kinase deficiency of mice associated with nonspherocytic hemolytic anemia and cure of the anemia by marrow transplantation without host irradiation.

Mutant mice with splenomegaly and nonspherocytic hemolytic anemia were found in an inbred colony of the CBA/N (hereafter CBA) strain maintained in the Japan SLC Haruno farm (Shuchi-gun, Shizuoka, Japan). The activity of pyruvate kinase (PK) in red blood cells (RBCs) of the anemic mutants decreased to 16.2% of normal (+/+) CBA mice. Because the mutant CBA mice showed a remarkable reticulocytosis (41.6%) and because the PK activity of reticulocytes is much higher than that of mature RBCs, the PK activity in mature RBCs of the mutant CBA mice was calculated to be 2.8% that of mature RBCs of CBA-(+/+) mice. Because RBC type PK is encoded by the Pk-1 locus of the mouse (chromosome 3), we designated the mutant locus as Pk-1slc. The anemia and PK deficiency of CBA-Pk-1slc/Pk-1slc mice were cured by bone marrow transplantation (BMT) from CBA-(+/+) mice. Prior irradiation was not necessary for the curative BMT. On the other hand, the BMT from CBA-Pk-1slc/Pk-1slc mice to nonirradiated CBA-(+/+) mice did not result in the decrease of RBCs and the reduction of PK activity. The present results indicate that CBA-Pk-1slc/Pk-1slc mice are a potentially useful animal model for studying pathophysiology of PK deficiency and for developing new therapeutic methods to correct PK deficiency.

Anemia, Hemolytic, Congenital Nonspherocytic↗

PubMed1995

Characterization of c-kit-positive neurons in the dorsal root ganglion of mouse.

Previously, we showed that c-kit receptor tyrosine kinase is expressed by a subpopulation of dorsal root ganglion (DRG) neurons, and that the ligand for the c-kit receptor, stem cell factor (SCF), induces the neurite outgrowth and supports the survival of these neurons in culture [16]. However, it is unknown which class of DRG neurons express c-kit receptor and which factor regulates differentiation and survival of c-kit-positive neurons. In the present study, we attempted to characterize c-kit positive neurons in the mouse DRG. The c-kit-positive neurons were small or medium in size, and 44% of these neurons contained substance P. Central fibers of the c-kit-positive neurons terminated in laminae I and II of the gray matter of the spinal cord. These results suggest that c-kit-positive neurons in the DRG belong to a functional subpopulation. The c-kit receptor protein was presented on the membrane of processes and growth cones in neurons. When DRG cells of embryonic day 15.5 or 17.5 were cultured, the survival of c-kit-positive neurons was supported by SCF, nerve growth factor (NGF) or leukemia inhibitory factor. SCF and NGF synergistically supported the survival of c-kit-positive neurons at submaximal concentrations. c-kit-positive DRG neurons from neonatal mice survived without addition of any factor in culture, suggesting that the requirement for trophic support in c-kit-positive neurons changes during development.

Age Factors↗

PubMed1995

Infection with Nippostrongylus brasiliensis induces invasion of mast cell precursors from peripheral blood to small intestine.

Precursors of mast cells were defined as cells that formed mast-cell colonies in methylcellulose culture (CFU-mast). Mononuclear cells (MNC) were obtained from the bone marrow, peripheral blood, and small intestine of Ws/Ws rats with a small deletion at the tyrosine kinase domain of c-kit and of control normal (+/+) rats. In the culture containing concanavalin A-stimulated spleen cell conditioned medium (ConA-SCM) alone, the numbers of mast-cell colonies produced by Ws/Ws MNC were comparable with those of +/+ MNC. In the culture containing both ConA-SCM and stem cell factor (a ligand of c-kit), however, the numbers of mast-cell colonies produced by +/+ blood MNC were 107 times as great as that of Ws/Ws blood MNC. Using this culture condition, we investigated changes in concentration of CFU-mast in the marrow, blood, and intestine of +/+ rats after infection with Nippostrongylus brasiliensis (NB), which induced marked mast-cell accumulation in the small intestine. The concentration of CFU-mast in blood dropped to 21% of preinfection levels 1 week after the NB infection. In contrast, a sevenfold increase of CFU-mast occurred in the small intestine. The proportion of CFU-mast in S phase of the cell cycle remained at low levels in the marrow and blood after NB infection, but it increased significantly in the small intestine. The present result suggests that NB infection induces the invasion of CFU-mast into the intestine from blood and their subsequent proliferation in the tissue site.

Animals↗

PubMed1995

Brain histaminergic system in mast cell-deficient (Ws/Ws) rats: histamine content, histidine decarboxylase activity, and effects of (S) alpha-fluoromethylhistidine.

The mast cell-deficient [Ws/Ws (White spotting in the skin)] rat was investigated with regard to the origin of histamine in the brain. No mast cells were detected in the pia mater and the perivascular region of the thalamus of Ws/Ws rats by Alcian Blue staining. The histamine contents and histidine decarboxylase (HDC) activities of various brain regions of Ws/Ws rats were similar to those of +/+ rats except the histamine contents of the cerebral cortex and cerebellum. As the cerebral cortex and cerebellum have meninges that are difficult to remove completely, the histamine contents of these two regions may be different between Ws/Ws and +/+ rats. We assume that the histamine content of whole brain with meninges in Ws/Ws rats is < 60% of that in +/+ rats. So we conclude that approximately half of the histamine content of rat brain is derived from mast cells. Next, the effects of (S) alpha-fluoromethylhistidine (FMH), a specific inhibitor of HDC, on the histamine contents and HDC activities of various regions of the brain were examined in Ws/Ws rats. In the whole brain of Ws/Ws rats, 51 and 37% of the histamine content of the control group remained 2 and 6 h, respectively, after FMH administration (100 mg/kg of body weight). Therefore, we suggest that there might be other histamine pools including histaminergic neurons in rat brain.

Alcian Blue↗

PubMed1995

Inhibition of attachment between cultured mast cells and fibroblasts by phorbol 12-myristate 13-acetate and stem cell factor.

Cultured mast cells (CMC) derived from the bone marrow of mice express the receptor encoded by the W (c-kit) locus (W receptor), and the WCB6F1(+/+)-3T3 fibroblasts express the ligand encoded by the Sl locus (stem cell factor [SCF]). CMC attach to the fibroblasts through the W receptors and cell-bound SCF. We investigated the effect of phorbol 12-myristate 13-acetate (PMA) and recombinant murine SCF (rmSCF) on the attachment. PMA induced both the internalization and shedding of W receptors, whereas rmSCF induced only the internalization. Moreover, both PMA and rmSCF reduced the expression of c-kit mRNA levels in CMC. Addition of either PMA or rmSCF to the coculture of CMC and fibroblasts resulted in the inhibition of attachment. Since the magnitude of the attachment between CMC and fibroblasts may be manipulated by changing the doses of either PMA or rmSCF, the present experimental system may be useful as a model for the attachment between blood cells and stromal cells.

3T3 Cells↗

PubMed1994

Characterization of cultured mast cells derived from Ws/Ws mast cell-deficient rats with a small deletion at tyrosine kinase domain of c-kit.

The Ws mutant allele of rats represents a 12-base deletion at the tyrosine kinase domain of the c-kit gene. Although homozygous Ws/Ws rats were deficient in both connective tissue-type mast cells (CTMC) and mucosal-type mast cells (MMC), mast cells did develop when bone marrow cells of Ws/Ws rats were cultured in the presence of concanavalin A-stimulated spleen cell conditioned medium (ConA-SCM). Although the proliferative response of rat cultured mast cells (RCMC) derived from Ws/Ws rats to ConA-SCM was comparable to that of RCMC derived from control normal (+/+) rats, the proliferative response of Ws/Ws RCMC to rat recombinant stem cell factor (rrSCF; a ligand for the c-kit receptor tyrosine kinase) was much lower than that of +/+ RCMC. However, a slight c-kit kinase activity was detectable in Ws/Ws RCMC, and the proliferation of Ws/Ws RCMC was accelerated when rrSCF was added to ConA-SCM. Because CTMC contain rat mast cell protease-I (RMCP-I) and MMC contain RMCP-II, the phenotype of +/+ and Ws/Ws RCMC in various culture conditions was evaluated by immunohistochemistry of RMCPs. Both +/+ and Ws/Ws RCMC showed the MMC-like phenotype (RMCP-I-/II+) when they were cultured with ConA-SCM alone. Most +/+ RCMC and about half of Ws/Ws RCMC acquired a novel protease (RMCP-I+/II+) phenotype when they were cultured with rrSCF alone. However, because the number of Ws/Ws RCMC dropped to one-tenth in the medium containing rrSCF alone, the absolute number of Ws/Ws RCMC with the RMCP-I+/II+ phenotype did not increase significantly. The effect of rrSCF in inducing the novel phenotype was suppressed when ConA-SCM was added to rrSCF. In contrast, +/+ and Ws/Ws RCMC cocultured with +/+ fibroblasts showed the RMCP-I+/II+ phenotype even in the presence of ConA-SCM. Moreover, a fibroblast cell line derived from SI/SI mouse embryos that did not produce SCF did not support the survival of both +/+ and Ws/Ws RCMC but did induce the RMCP-I+/II+ phenotype in about half of +/+ and Ws/Ws RCMC when their survival was supported by the addition of ConA-SCM. The normal signal transduction through the c-kit receptor did not appear to be prerequisite for the acquisition of the RMCP-I+/II+ phenotype.

Animals↗

PubMed1994

Strial dysfunction in a melanocyte deficient mutant rat (Ws/Ws rat).

A homozygous mutant rat at the white spotting (Ws) locus showing a deficiency of melanocytes has recently been found (4, 5). The function and morphology of the inner ear of the Ws/Ws rat were examined by auditory brainstem response (ABR), endocochlear DC potential (EP), and electron microscopy. The mean ABR threshold of the Ws/Ws rat was significantly higher than that of the control +/+ rat. Most Ws/Ws rats showed no or very little EP. In electron microscopy, the stria vascularis of the Ws/Ws rat proved to be very thin and flat with poor interdigitation of marginal cells, and absence of intermediate cells. The organ of Corti appeared to be intact in both the +/+ rat and the Ws/Ws rat. These electrophysiological and morphological findings suggest that the Ws/Ws rat suffered from severe hearing loss caused by strial dysfunction.

Acoustic Stimulation↗

PubMed1994

[Chronic empyema associated with large cell carcinoma of lung: case report with review of the literature].

A 71-year-old female was seen with a complaint of chest pain and cough, and a history of tuberculous pleurisy and artificial pneumothorax 40 years ago. The diagnosis of empyema with carcinoma was made by chest X-ray and CT scans. The examination of lung function showed a restrictive disorder. The value of the predicted postoperative FEV1 0.75 l encouraged to perform operation. A left pleuropneumonectomy and combined resections of the invasive portion of the pericardium and left atrium was performed. Histological examination revealed large cell carcinoma of lung (pT 4 N 1 M 0). The literatures are reviewed concerning the thoracic malignant tumor arising in chronic empyema cavity on Japanese cases.

Aged↗

PubMed1993

Age-dependent amelioration of hypoplastic anemia in Ws/Ws rats with a small deletion at the kinase domain of c-kit.

The white-spotting (Ws) locus of rats represents a 12-base deletion of the c-kit receptor tyrosine kinase. Homozygous Ws/Ws rats are deficient in melanocytes, mast cells, and erythrocytes. Although mice possessing two mutant alleles at the c-kit (W) locus, such as mice of W/Wv genotype, show severe anemia even in adult age, the anemia of Ws/Ws rats remarkably ameliorated with age. We investigated the mechanism of the age-dependent amelioration. Bone marrow cells of Ws/Ws rats did not form macroscopic colonies in the spleen of irradiated rats, and the concentration of burst-forming unit-erythroid in the marrow of Ws/Ws rats was comparable with that of +/+ rats. Therefore, the increase in morphologically identifiable erythroid precursors in the marrow of Ws/Ws rats was attributed to the increased concentration of colony-forming unit-erythroid (CFU-E). Furthermore, the increase in CFU-E appeared to result from the increased concentration of erythropoietin (EPO). Because injections of relatively low doses of EPO cured the slight anemia that remained in adult Ws/Ws rats, CFU-E and/or its immediate precursors of Ws/Ws rats appeared to be more sensitive to EPO than those of W/Wv mice, in which a huge dose of EPO was necessary to cure the anemia.

Age Factors↗

PubMed1993

Lethal effect of the anti-Fas antibody in mice.

During mammalian development, many cells are programmed to die most mediated by apoptosis. The Fas antigen coded by the structural gene for mouse lymphoproliferation mutation (lpr), is a cell surface protein belonging to the tumour necrosis factor/nerve growth factor receptor family, and mediates apoptosis. The Fas antigen messenger RNA is expressed in the thymus, liver, heart, lung and ovary. We prepared a monoclonal antibody against mouse Fas antigen, which immunoprecipitated the antigen (M(r) 45K) and had cytolytic activity against cell lines expressing mouse Fas antigen. We report here that staining of mouse thymocytes with the antibody indicated that thymocytes from the wild-type and lprcg mice expressed the Fas antigen, whereas little expression of the Fas antigen was found in lpr mice. Intraperitoneal administration of the anti-Fas antibody into mice rapidly killed the wild-type mice but neither lpr nor lprcg mice. Biochemical, histological and electron microscope analyses indicated severe damage of the liver by apoptosis. These findings suggest that the Fas antigen is important in programmed cell death in the liver, and may be involved in fulminant hepatitis in some cases.

Animals↗

PubMed1993

Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit.

All basophils, mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC) are derived from the multipotential hematopoietic stem cell. Mutations at the c-kit locus resulted in deficiency of MMC and CTMC in both mice and rats. To investigate the role of the c-kit receptor tyrosine kinase for production of basophils, we used white spotting/white spotting (Ws/Ws) mutant rats that have a small deletion at the tyrosine kinase domain of the c-kit gene. When Ws/Ws, nude athymic, and normal (+/+) rats were infected with Nippostrongylus brasiliensis (NB), the number of basophils increased greater than 50-fold in the peripheral blood of Ws/Ws and +/+ rats but did not increase in that of nude rats. Blood histamine concentration increased significantly in Ws/Ws and +/+ rats but did not increase in nude rats. Immature basophils increased greater than 10-fold in the bone marrow of Ws/Ws and +/+ rats but did not increase in that of nude rats. Mature and immature basophils that developed after the NB infection were identified by electron microscopy. The present result confirms that T-cell-derived cytokines are indispensable for the augmented production of basophils and suggests that stimulation via the c-kit receptor may not be necessary for the augmented production.

Animals↗

PubMed1993

Mast cell number in the skin of heterozygotes reflects the molecular nature of c-kit mutation.

The W locus of mice encodes the c-kit receptor tyrosine kinase. Heterozygous WJic/+ and Wn/+ mice and homozygous Wf/Wf mice were similar in appearance; all of them have large depigmented areas lacking any well-defined pattern. The WJic, Wn, and Wf mutant alleles were characterized and their molecular nature was correlated with the mast cell differentiation in the skin and the biologic features of cultured mast cell (CMC). All WJic, Wn, and Wf were point mutations at the tyrosine kinase domain, and c-kit mRNA was normally transcribed from all of them. The mature 145-Kd form of the c-kit protein was produced from the WJic and Wf alleles, but not from the Wn allele. c-kit proteins produced by the WJic or Wf allele were expressed on the surface of CMCs, but those of the Wn allele were not. When double heterozygous mice were produced between W and WJic and between W and Wn, both W/WJic and W/Wn mice lacked skin mast cells. W/WJic CMCs and W/Wn CMCs did not survive in the coculture with fibroblasts. W/WJic CMCs normally attached to fibroblasts, but W/Wn CMCs did not. The defect of W/Wn CMCs in the attachment was attributed to the deficient extracellular expression of the c-kit protein. The number of skin mast cells was compared among WJic/+, Wn/+, Wf/+, and Wf/Wf mice. Mast cells decreased in WJic/+ and Wf/Wf mice, but not in Wn/+ and Wf/+ mice. Although the Wn was a point mutation at the kinase domain, the biologic effect of the Wn was comparable with that of the W mutant allele, which produces truncated c-kit protein without the transmembrane domain. The weak phenotype of Wn/+ mice may be explained by the deficient extracellular expression of c-kit proteins produced by the Wn allele. When WJic/WJic, Wn/Wn, and Wf/Wf CMCs were stimulated by the recombinant c-kit ligand, autophosphorylation activity was observed only in Wf/Wf CMCs. This result was consistent with the weak biologic effect of the Wf mutant allele.

Adenosine Triphosphate↗

PubMed1993

Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cells in genetically mast cell-deficient Ws/Ws rats.

Ws/Ws rats have a small deletion at the tyrosine kinase domain of the c-kit gene and are deficient in both mucosal mast cells (MMC) and connective tissue-type mast cells (CTMC). The role of the c-kit receptor in the development of MMC and CTMC was investigated by infecting Ws/Ws and control +/+ rats with Nippostrongylus brasiliensis (NB), which induces T-cell-dependent mast cell proliferation. Although mast cells did not develop in the skin of Ws/Ws rats, a significant number of mast cells developed in the jejunum after NB infection. These mast cells had the MMC protease phenotype (rat mast cell protease [RMCP] I-/II+) and lacked heparin because they were not stained with berberine sulfate. Globule leukocytes were also detected in the mucosal epithelium of these rats. However, the number of MMC and the serum concentration of RMCP II in NB-infected Ws/Ws rats were only 13% and 7% of those of NB-infected +/+ rats, respectively. A small number of mast cells also developed in the lung, liver, and mesenteric lymph nodes of Ws/Ws rats after NB infection. Although mast cells in these tissues had the MMC phenotype throughout the observation period, the increased mast cells in the lung and liver of +/+ rats acquired a CTMC-like phenotype and were RMCP I+/II+, berberine sulfate+, and formalin resistant. These results indicate that the need for the stimulus through the c-kit receptor appears to be greater in the development of CTMC in the skin as well as for CTMC-like mast cells in the lung and liver than for the development of MMC.

Animals↗

PubMed1993

Development of mast cells and basophils: processes and regulation mechanisms.

Mast cells and basophils are offspring of the multipotential hematopoietic stem cell. Although mast cells sometimes are misunderstood as basophils that have invaded connective or mucosal tissue, these two kinds of basophilic cells are distinguishable by morphology and surface antigenicity. Developmental processes of mast cells and basophils are different. Basophils complete their differentiation within the bone marrow, but precursors of mast cells leave the bone marrow, invade connective or mucosal tissue, proliferate, and differentiate into mast cells. The mechanisms regulating development are different between mast cells and basophils. Both T cell-dependent and fibroblast-dependent mechanisms are involved in the development of rodent mast cells, but only the fibroblast-dependent mechanism is known for development of human mast cells and only the T cell-dependent mechanism for the development of basophils of both rodents and humans. The most important cytokine for the T cell-dependent mechanism appears to be interleukin-3, whereas for the fibroblast-dependent mechanism it appears to be the ligand for the c-kit receptor (ie, stem cell factor).

Animals↗

PubMed1993

Supernormal histamine release and normal cytotoxic activity of beige (Chédiak-Higashi syndrome) rat mast cells with giant granules.

The beige rat is an animal model of the Chédiak-Higashi syndrome. Since mast cells can be easily purified from the peritoneal cavity of rats, we investigated the function of beige rat mast cells with giant granules by using quantitative methods. Beige and normal rat mast cells were sensitized with anti-dinitrophenol (DNP) IgE antibodies and stimulated by DNP conjugated with human serum albumin. The proportion of histamine released to total histamine was significantly greater in beige rat mast cells than in normal rat mast cells. Since the supernormal histamine release of beige rat mast cells was observed after treatment with 12-O-tetradecanoylphorbol 13-acetate, calcium ionophore A23187, substance P or compound 48/80, it appeared to be attributable to the enlargement in granules in beige rat mast cells. Spontaneous cytotoxic activity of mast cells was assayed by incubating purified mast cells with 51Cr-labelled WEHI-164 cells. Both beige and normal rat mast cells showed significant cytotoxic activity, but no significant difference was detectable between beige and normal rat mast cells. Even after IgE-mediated stimulation, no significant difference in cytotoxic activity was detectable between beige and normal rat mast cells either. Giant granules of beige rat mast cells did not appear to influence the cytotoxic activity of mast cells.

Animals↗

PubMed1993

Stem cell factor induces outgrowth of c-kit-positive neurites and supports the survival of c-kit-positive neurons in dorsal root ganglia of mouse embryos.

The c-kit receptor tyrosine kinase is highly expressed by about 10% of the neurons in the dorsal root ganglia (DRGs) of mouse embryos. We investigated the in vitro effect of stem cell factor (SCF), the ligand for c-kit receptor, on DRGs. Recombinant murine SCF (rmSCF) induced the outgrowth of c-kit-positive neurites from DRGs of normal (+/+) embryos. The effect of SCF was dose dependent and completely abolished by anti-c-kit ACK2 monoclonal antibody (mAb). Some neurites whose outgrowth was induced by nerve growth factor (NGF) were c-kit-positive, but anti-NGF mAb did not inhibit the rmSCF-induced neurite outgrowth. rmSCF did not induce neurite outgrowth from DRGs of W/W embryos that did not express c-kit receptors on the cell surface and of W42/W42 mutant embryos that expressed c-kit receptors without tyrosine kinase activity. rmSCF also had a trophic effect on c-kit-positive neurons in the culture of dissociated DRG cells. Most c-kit-positive neurons appeared to respond to NGF as well, and the SCF-responsive subpopulation represented about 10% of NGF-responsive neurons. rmSCF did not support the survival of DRG neurons from embryos of W/W and W42/W42 genotypes. These results suggest that the stimulus through the c-kit receptor tyrosine kinase has an important role in development of the peripheral nervous system.

Animals↗

PubMed1993

Absence of immature mast cells in the skin of Ws/Ws rats with a small deletion at tyrosine kinase domain of the c-kit gene.

Ws/Ws rats have a small deletion at the tyrosine kinase domain of the c-kit gene, and practically no mast cells were detectable when the tissues were stained with alcian blue. Because alcian blue stains proteoglycans, there is a possibility that immature mast cells that do not contain a sufficient amount of proteoglycans are not detectable by this method. We examined this possibility by using other markers of mast cells. The histamine content in the skin of Ws/Ws rats was 0.3% that of control normal (+/+) rats. Because the number of alcian blue-positive mast cells in the skin of Ws/Ws rats was also 0.3% that of +/+ rats, histamine in the skin seemed to be concentrated to alcian blue-positive mast cells. Mast cells in the skin of +/+ rats express messenger RNA of Fc epsilon RI beta-subunit and c-kit protein. Because c-kit messenger RNA was normally expressed at least in the brain of Ws/Ws rats despite the small deletion, we examined the expression of Fc epsilon RI beta-subunit and c-kit messenger RNA in the skin and stomach of Ws/Ws rats by reverse transcriptase modification of polymerase chain reaction. Expression of either Fc epsilon RI beta-subunit or c-kit messenger RNA in the skin and stomach of Ws/Ws rats was estimated to be less than 1% that of +/+ rats. Moreover no Fc epsilon RI beta-subunit-expressing and no c-kit-expressing cells were detectable in the skin of Ws/Ws rats by in situ hybridization histochemistry. The present result suggests the absence of immature mast cells in tissues of Ws/Ws rats.

Animals↗

PubMed1993

Deficient differentiation of mast cells in the skin of mi/mi mice. Usefulness of in situ hybridization for evaluation of mast cell phenotype.

The staining property of skin mast cells changed from Alcian blue+/berberine sulfate- to Alcian blue+/berberine sulfate+ in the skin of normal (+/+) and Wv/Wv mice. In contrast, this change did not occur in the skin of mi/mi mice. Heparin content and histamine content per a mi/mi skin mast cell were estimated to be 34% and 18% those of a +/+ skin mast cell, respectively. The low heparin content of mi/mi skin mast cells seemed to be consistent with the Alcian blue+/berberine sulfate- staining property. Expression of genes encoding mast cell-specific proteolytic enzymes was examined by Northern blotting and in situ hybridization. Messenger RNA of mast cell carboxypeptidase A was expressed most of all by +/+, Wv/Wv, and mi/mi skin mast cells, but mRNA of mouse mast cell protease (MMCP)-6 was expressed by approximately a half of +/+ and Wv/Wv skin mast cells and by only 3% of mi/mi skin mast cells. A significant amount of MMCP-2 mRNA was not expressed in the skin of all +/+, Wv/Wv and mi/mi mice. This shows the presence of at least three phenotypes in skin mast cells of mice: berberine sulfate+/MMCP-6+, berberine sulfate+/MMCP-6-, and berberine sulfate-/MMCP-6-. The in situ hybridization of mRNA of mast cell-specific proteolytic enzymes seemed to be useful to describe abnormalities of mast cell differentiation in the skin of mi/mi mice.

Animals↗