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The differences in electrophoretic patterns of major urinary proteins (MUP's) due to sex, strain, and subspecies of the mouse (Mus musculus) were examined by the combined methods of agarose gel electrophoresis and immunofixation. The MUP's from the male of common laboratory inbred mice (M. m. domesticus) showed a component that was absent in females of the same strain, in addition to a strain-specific component that was determined by the Mup-1 allele carried by the strain. In MOA mice, an inbred strain from M. m. molossinus (Japanese wild mice), there was no apparent sex difference in the constitution of the components. The MUP's from this strain contained a major component that was virtually absent in those from laboratory mice, but lacked the strain-specific components of laboratory mice. In addition, the present methods revealed that both liver and serum contained MUP's consisting of components similar to those found in the urine from the same sex and strain.

Skin biopsy specimens from 24 patients with different lichenoid skin diseases that had been proved histologically were studied immunohistologically. Marked differences were noted in the number of OKT6+/S100+ Langerhans cells within the epidermis and dermis in the lesional skin between lichen planus (and its related disease) and lupus erythematosus; in the former these cells were increased in number; in the latter they were decreased in number compared with those in uninvolved perilesional skin. Human lymphocyte antigen (HLA)-DR expression on keratinocytes was observed not only in lichenoid skin diseases but also in control cases without epidermal involvement. In the two cases of systemic lupus erythematosus, the uninvolved perilesional skin also show weak and focal HLA-DR reactivity in the basal layer. HLA-DR+ keratinocytes could play an important role at least in the perpetuation of epidermal cell damage mediated by T cells.

A structural locus (C-6) for the sixth component of complement in mice is assigned to chromosome 15. Three-point linkage analysis indicated that the order of loci is C-6, Gpt-1, Gdc-1, and that the map distances are 25.9 +/- 4.9 between C-6 and Gpt-1, and 36.4 +/- 5.5 between C-6 and Gdc-1. Since Gdc-1 is more distal than Gpt-1, and C-6 is 26 cM away from Gpt-1, it is estimated that the C-6 is proximal to the centromere. In addition, a new C6 form found in AKR mice is described. We propose the designation C6B for it and C-6b for the allele encoding C6B.

To improve the production system, the onset and the termination of reproductive life of C3Hf/HeMsNrs mice mated immediately after weaning and reared for 400 days of life, were studied. From weaning females mated with a full grown male (group A), the first litter was obtained at a mean age of 47 days, suggesting the first copulation at 26 days of age. The age of males at the first copulation was estimated to be at 44 days of age from the age giving the first litters in weanling males mated with weanling (group B) and full grown (group C) females. The sex ratio of litters delivered by young dams tended to be excess in males. The reproductive performance of dams in later life was not affected by the parturition in earlier age. The production efficiency with weaned youngs per pair during the first 200 days after mating was the highest in group A. It was found from these results that the C3H females attained their sexual maturity at 5 to 6 days after weaning, being available for breeding without any deletion in reproductive performance.

Various T-cell surface molecules are involved in T-cell adhesion, which is an essential requirement for epidermotropic migration of T cells. Our previous studies demonstrated that certain T-cell clones can migrate into the epidermis upon their intradermal inoculation into the footpads of recipient mice with relevant antigens, while other T-cell clones, despite their identical antigen specificities and functions, are non-epidermotropic. We therefore tested whether the differences in epidermotropism of these T cells could reside in the different levels of expression of T-cell surface molecules such as CD3, CD4, CD2, and lymphocyte function associated antigen 1 (LFA 1). The results of flow cytometric analysis showed that LFA-1 was preferentially expressed on the surface of epidermotropic T-cell clones, while non-epidermotropic T-cell clones were negative or very weakly positive for LFA-1 with one exception. After exposure to phorbol ester, epidermotropic clones with high levels of LFA-1 did not show any further up-regulation of LFA-1. In contrast, under identical conditions, significant up-regulation of LFA-1 was observed on non-epidermotropic T cells with low levels of LFA-1. However, even after exposure to phorbol ester, these T cells remained non-epidermotropic. These results suggest that the presence of high levels of LFA-1 on T cells is absolutely necessary for their epidermotropic migration, but its up-regulation is neither necessary nor sufficient to trigger the epidermotropic migration. High levels of LFA-1, regardless of cell activation, may be required to mediate stable cell adhesions leading to epidermotropic migration.

In order to clarify the role of immunity on the development of dermatitis in NC mice, the following experiments were carried out. In neonatal thymectomized NC, thymic reconstituted NC-nu/nu, and passively serum transferred NC-nu/nu mice, incidence of the dermatitis was examined. Immune response to sheep red blood cells (SRBC) and number of Thy-1 positive cells in mesenteric lymph node were used as indicators of the cell mediated immunity. Although antibody to SRBC and the number of Thy-1 positive cells in neonatal thymectomized NC mice were greatly reduced, development of the dermatitis in these mice was not suppressed at all. On the contrary, thymic reconstituted NC-nu/nu mice which recovered immune response to SRBC and number of Thy-1 positive cells to the normal levels did not develop the dermatitis. Passive transfer of the serum obtained from NC mice which developed severe dermatitis, could not induce the dermatitis in NC-nu/nu mice. These results suggest that the dermatitis in NC mice is not mediated by immune mechanisms but by other complexed factors. The absence of the dermatitis in NC-nu/nu mice may be due to nu gene effects other than those of immune defect.

Two types of liver-specific F antigen in mice were distinguished by an immunoblotting technique after IEF of liver extracts. The IEF banding patterns consist of several bands whose pI vary from 7.57 to 8.15. One type of antigen (designated F2 antigen) showed a pattern that lacked some basic bands which are present in the pattern of the other type of antigen (designated F1 antigen). The latter type was found in AKR, CBA, C3H, DBA/2, and SM strains, while the former type was found in A, C57BL, and many other strains. Breeding experiments indicated that this variation is controlled by a single autosomal locus designated Laf (liver antigen F). Linkage analysis showed that the Laf locus is linked to the Pgm-1 locus on chromosome 5. The recombination frequency between these two loci is estimated to be 0.173 +/- 0.037. The distribution of F1 and F2 antigen types among inbred strains is concordant with that of type 1 and type 2 F antigens, which have been previously distinguished by their immunogenic differences, i.e., whether alloimmunization with the liver extracts from a given strain of mice can produce the antibody to F antigen in certain strains of mice. It is suggested, therefore, that the Laf locus may encode an allogeneic moiety of F antigen molecules.

A patient who for 26 years had common warts, which were resistant to various treatment modalities, was treated with a single intralesional injection of interferon-gamma after dinitrochlorobenzene immunotherapy, because immunologic studies indicated she had failed to respond to prior treatment modalities as a result of a functional impairment of her cellular immune response. Within 1 to 2 days, not only the wart injected with interferon-gamma, but also other warts, became erythematous and swollen, giving a lichen planus-like appearance. Without additional injections of interferon-gamma, all warts disappeared completely, leaving slight pigmentation. Interferon-gamma would be most effective when used with, rather than instead of, other immunotherapy.

Because of the similarity of their allelic profiles it was assumed that 'ICR' non-inbred mouse colonies were of common origin: however there were differences in allelic frequencies between them. It was also found that the allelic frequency a the C3-1 locus differed between samples from the same colony. Research workers should therefore be aware that the genetic variability of outbred animals may vary among samples, even if the animals are properly designated and supplied from the same breeder.

The coexistence of psoriasis and lichen planus has been rarely reported, although both diseases are relatively common and have some features in common. A rare case of simultaneous occurrence of both diseases is presented. Spontaneous improvement of psoriasis occurred during the development of lichen planus and a subsequent disappearance of the lichen planus was associated with an exacerbation of the psoriasis. The clinical courses of the two diseases may not be independent of each other, but be affected by common factors. Immunohistochemical studies with lesional skin suggested local production of interferon-gamma, which may in part explain the improvement of the psoriasis during the development of lichen planus. Based on these immunohistochemical findings, we discuss a putative role for these lymphokines in the pathogenesis of the two diseases.

Backcross progeny, (NC X TF/GnLe)F1 X TF/GnLe, was tested for C3 allotype controlled by C3-1 and the expression of mutant gene tf, repeated loss and regrowth of hair. The recombination frequency between these two loci both located in chromosome 17 of the mouse was 24%. Taken together with our previous linkage data, C3-1 is now localized to a position 11 cm more distal than H-2 on chromosome 17.

The presence or absence of the Es-Si esterase (female specific sex-influenced esterase) in rat sera was reexamined by the zymogram technique using agarosegel electrophoresis. It was found that female rat sera of the BN/Kyo strain, which has been typed as the Es-Si esterase negative, display an esterase migrating between the Es-1A esterase and the Es-2C esterase. Using a specific alloantibody to the esterase, it was shown that this esterase is identical to the Es-Si esterase. Thus, BN rats are the first described inbred rats possessing the Es-Si esterase, as well as the Es-1A esterase. Mating experiments between BN rats and SHR rats confirmed a previous demonstration that the presence or absence of the Es-Si esterase is controlled by a single gene locus closely linked to the Es-2 locus where the Es-1 locus also is linked. A further survey with 39 strains by the present methods revealed that besides two sublines of the BN strain, E3/Han, LOU/Max and PVG/Max strains also possess both the ES-1A esterase and the Es-Si esterase. The results indicate that these esterases are controlled by separate gene loci.

A new method has been proposed for detection of lac color in food. Lac color is a natural color additive derived from a secretion of the insect Coccus Laccae (Laccifer lacca Kerr). It is extracted from food with methanolic oxalic acid and eluted from a column of Amberlite XAD-2 with the same solvent. The fraction containing the lac color is treated with diazomethane to produce 2 reddish-orange markers. The marker species in the reaction mixture are detected by both thin-layer chromatography and reverse-phase liquid chromatography.

The sex-limitation of sex-influenced esterase (ESSI) in serum of rats carrying Es-Sia allele was re-examined. ESSI was detected in immature males and females, and orchiectomized rats as well as mature females whereas ESSI in normal males rapidly disappeared with puberty. The rats orchiectomized at weaning temporarily lost ESSI around the age of sexual maturation, thereafter, ESSI reappeared. When orchiectomized rats were administered testosterone, synthesis of ESSI was suppressed as in normal adult males. Effect of ovariectomy was not recognized. The exceptional strain named SI 3 of which normal mature males have a significant level of ESSI has been established, although the level in the males is lower than that in the females of the same strain.

The present study showed that the presence or absence of a new component of major urinary proteins (Mups), which is found in MOA mice, an inbred strain of Mus musculus molossinus (Japanese wild mice), is controlled by a single codominant gene locus. The linkage analysis shows that the locus is on chromosome 4, where the Mup-1 locus is assigned; its alleles, Mup-1a, and Mup-1b determine two phenotypic forms of MUPs in laboratory mice (M. m. domesticus). Recombination values between the locus and other loci on chromosome 4, such as brown (b), Pgm-2, and Gpd-1 are compatible with the gene order, Mup-1-b-Pgm-2-Gpd-1, on chromosome 4. Thus, it is concluded that the locus is identical to Mup-1 and it is proposed that Mup-1c be designated as the allele that determines a third phenotypic form of MUPs in MOA mice.

An antiserum to a serum protein from female ACI rats was produced in DONRYU rats by alloimmunization. The serum protein reacting with this antiserum was shown to be a sex-influenced esterase which is identified by zymogram techniques. Evidence for this is as follows: this protein migrated in the albumin region on agarose gel immunoelectrophoresis and was not present in sera from mature males; all rats possessing the protein were sex-influenced esterase in sera specifically disappeared after treatment with this antiserum. The attempt in ACI rats to produce antiserum to the esterases from DONRYU rats was unsuccessful.

The number of mast cells in connective tissue from dorsal skin varied markedly among mouse strains. Inbred strains of mice were typed into three groups, high (NC and NZB mice), low (B6, B10, and BALB/c mice), and intermediate (C3H/He and DBA/2 mice), by their mast cell content in the skin. However, the strain differences in the number of mast cells was marginal at the age of weaning but became distinct with age. This could be explained mainly by the frequently observed clustering of mast cells in adult NC and NZB mice and the rarely observed clustering in younger mice as well as in adult B10 and BALB/c mice. The breeding experiment revealed that the difference in the number of mast cells between NC and B10 mice was controlled by a single autosomal dominant locus, for which we propose the designation Mcr (mast cell regulator). The role of the Mcr locus with regard to the frequency of the mast cell population in connective tissue is discussed.

We have previously demonstrated that anti-H-43a CTL response of H-43b responder mice was exclusively restricted by self H-2Kb (Kb) but not by the other nine self MHC class I alleles from independent origins, i.e., Kbml,d,k,s and Db,d,k,q,s. In the present study, we verified that Kf,q,r and Df,r alleles could also not serve as restricting class I elements in the CTL response to H-43a alloantigen. Another notable observation made in the earlier study was the fact that, in H-43 incompatibility of the alternative combination, H-43a mice were incapable of generating CTL activity against H-43b alloantigen. However, by means of employing new in vivo immunization procedures, we discovered that some but not all genetically identical H-43a responder mice could mount anti-H-43b CTL response restricted by self Kb. Again, no anti-H-43b CTL activity could be generated in the context of self Kk, Kj, Db or Dk molecules. Although the number of class I alleles we examined is still limited, these results indicate that antigenic fragments derived from the processed H-43a and H-43b alloantigens possess an indistinguishable epitope (agretope), and that such agretope either interacts only with the privileged Kb molecules or allows to bestow the immunogenic conformation of allodeterminants on the fragments solely in the context of the restricting Kb element.

Structural polymorphism of murine factor H protein was demonstrated by using three different methods. 1) By prolonged agarose electrophoresis and immunofixation, factor H protein was visualized in the beta region as a single, distinct protein band in freshly bled EDTA-plasmas from many laboratory and wild mice. Two variants were detected among a large number of tested strains; one, referred to as H.1, moved faster to the anodal region (type strain, BALB/c), and the other, referred to as H.2, moved more slowly to the anodal region (type strain, STR). The F1 hybrid between BALB/c and STR exhibited a combining type of factor H protein, which was observed in each parent. 2) Two-dimensional peptide mapping analysis was carried out with tryptic peptides of these two factor H allotypes. Almost all of the spots in the maps of tryptic peptides were common to both allotypes. However, three distinct spots among the 57 spots detected in the map of tryptic peptides of the H.1 allotypes were not detected in that of H.2 allotype, whereas two spots among the 56 spots in the map of H.2 allotype were unique for this allotype. The F1 hybrid between BALB/c and STR showed a combining type of the map of parent. 3) Alloantisera against each of H allotypes were successfully produced in BALB/c or BALB/c-H.2 (a congenic strain with H.2 allotype) by repeated injection of each purified factor H protein either from the BALB/c or the STR strain. These findings indicated that the observed variants of factor H represent antigenically and structurally distinguishable allotypes. The allotypes of murine factor H protein are controlled by a single codominant locus located between the Hc locus and the beta 2M locus on the second chromosome of the mouse. This was shown by phenotyping the Hc locus and H locus with backcross progenies between A/J (one of strain with H.1) and MoA (one of strain with H.2). The recombination frequency between these two loci was 0.17 +/- 0.046.

Antigenic specificities of a serum protein from the mouse Mol-A strain (a strain derived from the Japanese wild mouse, Mus musculus molossinus) was studied by gel precipitation with alloantisera produced by reciprocal alloimmunization between Mol-A and BALB/c mice. Alloantigens which migrate immunoelectrophoretically in the alpha region of serum proteins have also been identified. The evidence indicated that this antigenic specificity is controlled by a codominant autosomal locus designated Aph-1. The evidence also suggests that the Aph-1 locus is linked to the alpha locus on chromosome 2.

Muscular dystrophy was found in the SM strain of mice. This defect was shown to be caused by a single autosomal recessive gene allelic with the genes at the dy locus. The dystrophic SM mice may provide a useful animal model for human muscular dystrophy, because SM strain has been selected for small body size and carries rare alleles at several loci.