Nobumoto Miyashita

A new inbred strain JF1 established from Japanese fancy mouse carrying the classic piebald allele

A new inbred strain JF1 (Japanese Fancy Mouse 1) was established from a strain of fancy mouse. Morphological and genetical analysis indicated that the mouse originated from the Japanese wild mouse, Mus musculus molossinus. JF1 has characteristic coat color, black spots on the white coat, with black eyes. The mutation appeared to be linked to an old mutation piebald (s). Characterization of the causative gene for piebald, endothelin receptor type B (ednrb), demonstrated that the allele in JF1 is same as that of classic piebald allele, suggesting an identical origin of these two mutants. Possibly, classic piebald mutation was introduced from the Japanese tame mouse, which was already reported at the end of the 1700s. We showed that JF1 is a useful strain for mapping of mutant genes on laboratory strains owing to a high level of polymorphisms in microsatellite markers between JF1 and laboratory strains. The clarified genotypes of JF1 for coat color are “aa BB CC DD ss”.

A Hybrid Origin of Japanese Mice "Mus musculus molossinus"

Taxonomy of the house mouse, Mus musculus is currently being extensively discussed. Feral and commensal forms of Mus musculus provide an important pool of genes (Morse 1978). In order to unify the taxonomy of the species, it is necessary to accumulate and integrate many lines of experimental evidence. The information on Asiatic mice is still incomplete.

Genetic Features of Major Geographical Isolates of Mus musculus

Laboratory mice have greatly contributed to the remarkable advances in immunogenetics and mammalian molecular genetics for the last decade. At present many different mouse strains, both classical and newly developed, are available for genetic studies. It is quite reasonable with the extensive development of research in this field, that one would like to know the natural origin of laboratory mice based on their genetic constitution. We have already revealed that the mitochondrial genome and most of the nuclear genomes of the present laboratory mice originated from an European subspecies Mus musculus domesticus (Yonekawa et al 1980, 1982; Moriwaki et al 1982, 1985). From mtDNA sequences, Ferris et al (1982) suggested “Common laboratory strains of inbred mice are descended from a single female”. From stand points of either immunogenetics, molecular genetics or evolutionary genetics, it should be desirable to increase further the genetic diversity of the laboratory mice. This could be achieved by utilizing other mouse subspecies. Schwarz and Schwarz (1943) taxonomically discriminated 15 subspecies of mice of Old World origin.

Allelic constitution of the hemoglobin beta chain in wild populations of the house mouse, Mus musculus

We studied the allelic frequency of the hemoglobin beta chain (Hbb) of wild mice, Mus musculus, collected from 46 localities, mostly in Asia and surrounding areas. The wild populations in the northern part of China, Korea, and the central part of Japan exhibited an almost monomorphic distribution of Hbbp. In the southern part of Asia, the frequency of Hbbp decreased and Hbbd was predominant. Although Hbbs and Hbbd are generally found in Europe, the Hbbp allele was present in Southeastern Europe (Bulgaria). In the light of these results, the Hbbp allele might have originated in mice of northern Asia.

Serological survey of T-lymphocyte differentiation antigens in wild mice

Allelic distributions of Thy-1, Ly-l, and Ly-2 antigens in wild mice are characteristic of each Mus musculus subspecies. Eastern mice (M.m.molossinus, M.mmusculus, M.m.castaneus, M.m.bactrianus) express the Thy-1.1 antigen, whereas Western mice (M.m. domesticus, M.m.brevirostris) express the Thy-1.2. All mice from wild populations examined in this survey express the Ly-1.2. The Ly-2.1 is distributed in Eastern mice and some Western mice, and the Ly-2.2 is found in the remaining Western mice. Allelic distributions of these antigens were also examined in two other species, Mus spretus and Mus spicilegus. Allelic constitutions of Thy-1 and Ly-1 in these species are similar to those of Eastern mice. Some M.spicilegus, however, express the Ly-1.1 antigen. This antigenic type is not found in M.musculus. Some Eastern mice related to M.m.castaneus react weakly to Ly-1.2-specific and Ly-2.1-specific monoclonal antibodies in both the complement-mediated cytotoxicity test and the absorption test. These results suggest that M.m.castaneus has unique alleles in the Ly-1 and Ly-2 loci.

Seroepidemiological survey of lymphocytic choriomeningitis virus in wild house mice in China with particular reference to their subspecies.

Serum samples from 337 wild house mice (Mus musculus) from 35 sites in China, collected in 1992 and 1993, were examined for antibodies against lymphocytic choriomeningitis virus (LCMV). Ten samples from eight sites were found to contain such antibodies. Six of the eight positive sites were located in the territory of M. m. gansuensis. One of the other two sites was located in the territory of M. m. castaneus in southern China and the other site was in a habitat of M. m. castaneus which had invaded into the western end of the territory of M. m. homourus. It seems likely that LCMV is distributed in the territories of M. m. gansuensis and M. m. castaneus in China. This is the first report of detection of these antibodies in wild house mice in China and specifically in the territories of M. m. gansuensis and M. m. castaneus.

Evolutionary relationships between laboratory mice and subspecies ofMus musculus based on the restriction fragment length variants of the chymotrypsin gene at thePrt-2 locus

Restriction endonuclease fragment length variants in mice were compared by Southern blot analysis using the cDNA probe pcXP33 for the chymotrypsin gene. The variants were detected in the restriction patterns generated by fragments from digestions withBglII,EcoRI,HindIII,Pstl,SacI, andXbaI. The set of protein phenotypes and the restriction patterns of chymotrypsin gene were examined in many laboratory strains and wild subspecies. Most laboratory strains (26 strains) are grouped into a set defined as Set 1, but only a few laboratory strains (AU/SsJ and five BALB/c sublines) are classified as belonging to Set 2. Of wild subspecies, only BRV-MPL (M. brevirostris) can be placed in Set 1, while DOM-BLG and SK/Cam (M. domesticus) belong in Set 2. The assignment of an appropriate set defined by the characteristics of the chymotrypsin gene has also been investigated inM. musculus, two Chinese subspecies,M. yamashinai, M. molossinus, andM. castaneus, and the evolutionary relationship between laboratory mice and various subspecies ofMus has been examined.

The H-2 class II genes and the susceptibility to the development of pulmonary adenoma in mice.

To determine the locus in theH-2 complex that affects susceptibility to the development of pulmonary adenomas in mice,H-2 congenic and recombinant strains of mice with A/Wy, BALB/c, C3H, and B10 backgrounds were subjected to treatment with urethane. The average number and the incidence of adenoma foci were recorded five months after the treatment. InH-2 congenic strains on the A/Wy background, the average number of adenoma foci per mouse was significantly higher in mice of the A/Wy, A/J, and A-Tlab (H-2a) strains than in A.BY (H-2b) mice. In BALB/c and C3H congenic strains, the strains carrying theH-2k haplotype were more susceptible than those carrying theH-2b haplotype. InH-2 congenic strains on the B 10 background, the average number and incidence of foci was also higher in haplotypesa, h2, k, andj than in haplotypesb, s, f, d, r, h4, i3, i5, and4. The average numbers of adenoma foci in (A/J × A.BY)F1 (H-2a/H-2b) and (B10 × B10.A)F1 (H-2b/H-2a) were intermediate between the numbers in the parental strains. In [B10.A (4R) × B10.A (3R)]F1 (H-2h4/H-2i3) and [B10.A (4R) × B10.A (5R)]F1 (H-2h4/H-2i5), the numbers of adenoma foci were higher than in resistant parental recombinants. These patterns of response to urethane matched the patterns of the immune response to lactate dehydrogenase-B (LDH-B) and immunoglobulin gamma 2a (IgG2a) proteins. These differences between mice in their susceptibility to the development of pulmonary adenomas is probably due to the polymorphism of the class II genes in theH-2 complex.

Methylation imprinting was observed of mouse mo-2 macrosatellite on the pseudoautosomal region but not on chromosome 9

Mouse mo-2 macrosatellites consisting of 31-bp tandem repeat units are mainly located at two loci in the C57BL/6 genome, one being at the centromere-distal telomeric region of chromosome 9 and the other at the pseudoautosomal (PA) region of chromosomes X and Y. The two clustes constitute approximately 300 kb and 150 kb, respectively. Southern analysis of a methylation-sensitive enzyme, HpaII-digested DNA showed that the mo-2 macrosatellites are detected as more than 30 polymorphic bands. Comparison of those bands between reciprocally crossed F1 mice revealed that approximately 20% of the allele-specific fragments exhibit different band intensities depending on the sex of the parent of origin. The differential methylation is observed in the mo-2 macrosatellite on the PA region but not in that on chromosome 9. Several fragments including the 3.4-kb fragment without internal HpaII site are more clearly detected when paternally derived, suggesting that the male-derived macrosatellite is undermethylated. Interestingly the difference is much more remarkable in inter-subspecific F1 mice between C57BL/6 and MSM than F1 between C57BL/6 and C3H/He. This suggests the presence of a modifier(s) that affect(s) the methylation of mo-2 in the MSM genome.

Evolutionary relationships between laboratory mice and subspecies of Mus musculus based on the genetic study of pancreatic proteinase loci, Prt-1, Prt-2, Prt-3, and Prt-6

Various patterns of mouse pancreatic proteinase activity bands were observed on agarose gel electrophoresis. Prt-1aand Prt-1bgenes control the positive (PRT-1A) and negative (PRT-1B) expression of tryptic band V, respectively; Prt-2aand Prt-2bcorrespond to chymotryptic bands II (PRT-2A) and III (PRT-2B); Prt-3aand Prt-3bcontrol the low (PRT-3A) and high (PRT-3B) tryptic activities of band IV; the Prt-1 and Prt-3 loci are closely linked on the same chromosome; Prt-6aand Prt-6bcorrespond to tryptic bands I (PRT-6A) and I′ (PRT-6B). Twenty-four laboratory strains from the United States showed the phenotype PRT-1A, PRT-3A, and PRT-2A. Of laboratory strains established in Europe, 6 showed PRT-1A, PRT-3A, and PRT-2A, and 10 had PRT-1B, PRT-3A, and PRT-2A bands. Most wild mice around the world and their descendants showed the phenotype PRT-1B, PRT-3B, and PRT-2A. Only the phenotype of M. m. brevirostris was PRT-1A, PRT-3A, and PRT-2A, which was the same as most laboratory inbred strains. PRT-2B was observed mainly in Japanese (M. m. molossinus) and Korean (M. m. yamashinai) wild mice. PRT-6B was detected only in Mus spicilegus and Mus caroli, but all other mice including wild populations and laboratory strains showed PRT-6A. New biochemical phenotypes such as PRT-2C and PRT-3C were also found in this study.