The increasing availability of molecular markers and the development of highly efficient gene mapping strategies for the mouse, rat and human genomes have generated vast quantities of information allowing for the progressive refinement of comparative maps. In this publication we report on an updated version of our rat/ mouse/human comparative genetic map, based on the mouse map. Databases for mouse, rat and human gene mapping were used for the collection of homologs mapped in the species. The comparative map was constructed with a total of 1,235 mouse loci having known homologs in the rat and/or human: 16 having homologs only in the rat, 884 having only in the human and 335 both in the rat and human. The combined length of the segments conserved between the rat and mouse spans 758 cM on the mouse map. This indicates that about 47% of the mouse genome is now covered by known rat homologous regions. Five novel regions homologous for the rat and mouse were identified. This comparative genetic map should be useful for researchers working on genetic studies in the rat, mouse and human.

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In 1991, several hairless offspring were found in our black haired KK (KK-C) mouse colony. This mutant, provisionally naming KK-rhino mouse was clinicopathologically and histopathologically investigated in a chronological manner. KK-rhino has a hairless trait and wrinkled and pimpled skin, which resemble the characteristics of the so-called rhino mouse. It was presumed from a preliminary mating examination that the trait of the KK-rhino mutant might be manifested by the [hr^rh] gene. Other properties of this mutant might be inherited from the maternal KK-C line. KK-rhino mouse is a unique mouse strain which has two quite different traits, "rhino" and "diabetes".

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Here we characterized macaque monkey CD4 by flow cytometry. The results showed that relatively lower fluorescence intensity was observed depending on the monoclonal antibodies (mAbs) used for staining; Leu-3a exhibited four-fold lower intensity than Nu-Th/i, and that formaldehyde fixation dramatically reduced fluorescence intensity of macaque CD4⁺ cells stained with Leu-3a but not of human cells. Nu-Th/i is therefore preferable for the analysis of macaque CD4. Pretreatment of either mAb inhibited the other mAb binding to human CD4. On the contrary, Nu-Th/i inhibited Leu-3a binding but Leu-3a poorly blocked Nu-Th/i binding to the macaque CD4. These results indicate that Leu-3a and Nu-Th/i epitopes are conserved in macaque CD4 but Leu-3a epitope is conformationally cryptic and/or fragile, resulting in the lower affinity. Amino acid sequence alignment of CD4 domain 1 shows that the substitutions outside the linear Leu-3a epitope may determine these characteristics of macaque CD4.

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Histological changes in the rat nipple during the reproductive cycle were observed. In virgin and the first half (days 5 and 10) of pregnancy, the nipple had a dull conical shape and the germinative layer of epidermis, thicker than that of the skin surrounding the nipple, deeply ingrew into the dermis in the basal region. From the second half (days 15 and 20) of pregnancy to the post-weaning period, the nipple appeared columnar in shape and many wrinkles were observed in the nipple wall especially during the lactating period. Collagen fibers longitudinally running in the nipple wall mainly comprised the dermis of the nipple and became loose during lactation. Small numbers of elastic fibers running parallel with smooth muscles were also observed in the nipple wall, and these increased in number and thickness from the second half of pregnancy, and most became frizzy structures during lactation. Around the lactiferous sinus, smooth muscle cells were arranged longitudinally but a few muscle cells were seen in a concentric layer, but during the lactating period the sinus was distended and many epithelial folds were observed. Morphometrical analysis indicated that the length of the nipple increased from the second half of pregnancy and reached the maximum on day 15 of lactation, approximately 3.7 times that in the virgin period. The outer diameter of the nipple and thickness of the nipple wall during lactation also reached approximately twice that in virgin. The size of the nipple decreased gradually after weaning. These observations suggest that the histological changes in the rat nipple during the reproductive cycle were mainly characterized by hyperplasia of the epidermis and hypertrophy of connective tissue in the dermis from the second half of pregnancy.

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In order to evaluate the availability of plasma amino acid (AA) concentration as a parameter to determine AA requirements of rats within a short period, the response of the plasma AA concentration to changes in dietary AA levels was studied. In Experiment 1, to clarify whether the plasma AA concentration responded to changes in dietary AA levels and how long the response of the plasma AA concentration was maintained, 10 male rats were fed a casein diet for a 7 day period, and then the food was changed to AA diets. The serine (Ser), glycine (Gly) and threonine (Thr) levels were decreased from 120, 90 to 60% of the casein diet at 7-day intervals successively. Blood samples were taken at 2, 4 and 7 days after changing the diet, from the vena caudalis by vein puncture. In all cases, the plasma AA concentration responded to changes in dietary AA within 2 days, and the response was maintained until the 7th day. Experiment 2 was conducted to confirm that the plasma concentration of each AA responded to the changes in dietary AA levels at the first day and the responses of the plasma concentration of AA were maintained until the 4th day after changing the dietary AA levels, when the combination of metabolically unrelated AA was added. Five rats in A groups were fed diets with added arginine + Thr, histidine + methionine, lysine or isoleucine + Ser, and five rats in B groups were fed diets with added Gly + valine, leucine + phenylalanine or Thr + tyrosine+valine for a 4-day period successively. Blood samples were taken at 1 and 4 days after changing diets. Although the plasma concentrations of histidine, leucine, methionine, phenylalanine and Ser did not respond to changes in dietary AA levels, those of other AA responded at 1 day and the responses were maintained until the 4th day.

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Male Syrian hamsters were exposed to smoke from three different types of cigarettes rated as mild, medium, and strong on the basis of their smoke chemistry for 4 weeks. These hamsters were euthanized at 0, 1 and 2 weeks of recovery after the last smoke exposure to study the pulmonary cell response after cessation of smoking. The free macrophage count determined on lung sections stained with hematoxylin and eosin was used as the index to evaluate the rate of recovery from smoke-related insult caused by the different types of cigarettes. The number of macrophages in the smoke-exposed hamsters was consistently greater throughout the recovery period than in the controls, depending on the amount of particulate components including tar and nicotine in the test cigarettes. The macrophage mobilization peaked at the first week of recovery and then showed a tendency to decrease at the second week. At the second week, however, the hamsters exposed to smoke from strong or medium cigarettes still showed significantly higher counts than the controls, while no significant change was noted in those exposed to smoke from mild cigarettes. These results indicate that the process and duration of recovery after cessation of smoking may depend on the extent of particulate matter impinging on the respiratory tract, so that strong cigarettes would be more hazardous because of greater number and longer retention of macrophages in the lung.

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TNF-α has been reported to be induced in mice infected with Sendai virus. We evaluated the role of TNF-α in the virus infection. TNF-α was induced locally in proportion to virus titers in the lung. The activity was correlated with suppression of body weight gain. Passive immunization against TNF-α improved body weight gain and ameliorated pneumonic lesions in infected mice, and prevented them from lethal infection, but lung virus titers were not affected by passive immunization. These results indicate that Sendai virus-induced emaciation, pneumonic lesions and death were mediated by TNF-α.

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Airway hyper-responsiveness is known as an important pathogenesis of asthma. In the present study, the airway responsiveness to aerosolized and injected histamine in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs was investigated. In addition, the role of the vagal reflex in histamine-induced airway contraction was evaluated by vagal blocking with atropine inhalation or bilateral vagotomy. A significantly higher bronchoconstrictive reaction, i.e., a decrease in tidal volume (V_T) and an increase in respiratory resistance (Rrs), to histamine-inhalation was observed in BHS than in BHR. A noticeably lower reduction in V_T was noted after atropine pretreatment for both BHS and BHR, whereas an increase in Rrs was inhibited only in BHS. The intravenous injection of histamine caused a noticeable bronchoconstrictive reaction in both BHS and BHR with a dose-dependent relationship, but no significant differences were observed and the bilateral vagotomy failed to induce any difference between the two animal groups. These results demonstrated that the airway responsiveness to histamine is considerably different in BHS from that in BHR, but the difference is largely dependent on the route of administration of histamine. The important role of the vagal reflex on the elicitation of airway contraction was elucidated in both animal groups, and it appeared that the BHS possessed relatively higher dependency on the vagal reflex mechanism than the BHR.

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A genetic typing method for the mouse and rat nude mutations by PCR and restriction fragment length polymorphism (RFLP) analysis was developed. Since restriction sites useful for RFLP analysis do not exist in the mouse nu and rat rnu mutations, artificial restriction sites were introduced by PCR with modified primers. Three genotypes in the mouse (nu/nu, nu/+ and +/+) or rat (rnu/rnu, rnu/+ and +/+) are rapidly differentiated with the PCR-RFLP assay. In addition, congenic nude strains can be efficiently established by using this assay. Finally, genetic mapping of the rnu locus was performed with microsatellite markers. The locus order on rat chromosome 10 was D10Mgh14-(2.0cM)-D10Mit2-(1.4cM)-rnu-(0.7cM)-D10Mgh6-(2.7cM)-D10Mit8.

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An acceleration of the elimination of transfused human (Hu) red blood cells (RBC) was found in C.B-17scid (SCID) mice that were kept in our facility. Yeast like organisms were isolated from their tap water just as a pure culture and the two isolates SW5 and SW6 were assigned to be Candida guilliermondii by analysing their generic small subunit ribosomal RNA sequences. To test whether the isolates are infectious in mice, we inoculated SCID and BALB/c mice orally with SW5 and observed them for 63 and 48 days, respectively. The yeasts were frequently recovered from oral swabs, feces and their tap water throughout the experiment. Although none of the mice developed clinical signs or histopathological changes, a positive sero-conversion was confirmed in 4 of 5 SW5-inoculated BALB/c mice. Moreover, a significant acceleration of Hu-RBC elimination in all of the SW5-infected SCID mice was demonstrated. We believe this to be the first report of an inapparent but significant outbreak of C. guilliermondii infection in mice.

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