Shigeo Honjo

Differentiation of mitochondrial DNA types inMacaca fascicularis

Restriction fragment length polymorphism in the mitochondrial DNA ofMacaca fascicularis from four geographical regions, Indonesia, the Philippines, Malaysia, and Indochina, was analyzed. In total, 21 types of mitochondrial DNA were detected using five restriction enzymes. These types were divided into two main groups based on phylogenetic analyses, one of which corresponded to the types of continental (Malaysia/Indochina) populations and the other to the types of a insular (Philippine) population. The types in the Indonesian population belonged to both groups. In the phylogenetic tree for the four populations, two clusters were constructed, one for the continental populations and the other for the insular ones.

Collagen-induced arthritis in nonhuman primates: Multiple epitopes of type I collagen can induce autoimmune-mediated arthritis in outbred cynomolgus monkeys

OBJECTIVE To define which regions of the type II collagen (CII) molecule result in anticollagen antibody production and the subsequent development of autoantibodies in a collagen-induced arthritis (CIA) nonhuman primate model. METHODS Male and female cynomolgus monkeys (2-6 of each sex per group) were immunized with either chicken (Ch), human, or monkey (Mk) CII, or with cyanogen bromide (CB)-generated peptide fragments of ChCII emulsified in Freunds complete adjuvant. Monkeys were observed for the development of arthritis, and sera were collected and analyzed for anticollagen antibody specificity by enzyme-linked immunosorbent assay. RESULTS Overt arthritis developed in all groups of monkeys immunized with intact CII and with all major CB peptide fragments of ChCII except CB8. Onset and severity of arthritis correlated best with serum anti-MkCII antibody levels. The levels of IgG autoantibody to MkCII were a result of the cross-reactivity rate of anti-heterologous CII antibodies with MkCII, which was based on the genetic background of individual monkeys rather than on sex differences. CONCLUSION CII from several species and disparate regions of the CII molecule were able to induce autoantibody-mediated arthritis in outbred cynomolgus monkeys. The strong anti-MkCII response suggests that epitope spreading or induction of broad-based CII cross-reactivity occurred in these animals. Autoantibody levels to MkCII were higher in CIA-susceptible monkeys than in resistant monkeys, despite comparable antibody levels in response to the various immunizations of CII. These results closely parallel the type of anticollagen responses found in sera from rheumatoid arthritis patients. Perhaps this can be accounted for by similar major histocompatibility complex heterogenicity associated with an outbred population, or maybe this is a primate-specific pattern of reactivity to CII.

Polymorphism in the mitochondrial DNA of cynomolgus monkeys

Variations in the mitochondrial DNA of a total of 150 cynomolgus monkeys (Macaca fascicularis) from Indonesia, the Philippines, and Malaysia were studied using a restriction endonuclease, EcoRI. Three distinct patterns were detected and they were denoted as morph 1, 2, and 3. The Malaysian population proved to be significantly different from the remaining two populations in the distributions of the three EcoRI morphs.

Human-type ABO blood groups as genetic markers for the management of a squirrel monkey (Saimiri sciureus) breeding colony

The human-type ABO blood groups were determined for 94 families of the squirrel monkey which included 151 animals. Four phenotypes of ABO blood groups (A, B, AB, and O) were detected. Family analysis revealed that the human-type ABO blood groups in this species were governed by three alleles, codominantA andB and silentO. There were intraspecific differences in the distribution of phenotypes and gene frequency among three populations imported by different routes at different times. The usefulness of ABO blood groups for defining the genetic variability of a squirrel monkey breeding colony through successive generations is discussed on the basis of the difference in distribution of ABO blood groups between wild-originated parental and its first colony-born populations.

Artificial Nursing of New-born Cynomolgus Monkeys as a Model of the Human Infant and Development of Abnormal Behavior

New-born cynomolgus monkeys were sucessfully reared by artificial nursing that was started just afterbirth with a 12% solution of a commercially prepared powdered-milk (Yukijirushi, P 7a) containing 13.3g of protein per 100g. Marked growth-retardation was observed in baby cynomolgus monkeys fed on a 12% solution of the modified P 7a milk containing only 6.6g of protein per 100g to which lactose was supplemented to give a baby monkey the same caloric value as that of the original P 7a milk. These artificially reared cynomolgus monkeys manifested various kinds of abnormal behavior such as self-clasping, autism-like self mouthing, huddling, stereotype rocking, head-knocking, autoerotism, fear, aggression, etc.. Generally, development of these abnormal behaviors was more noticeable in the monkeys nursed with a milk bottle fixed to the side of a cage without human contact than in the monkeys nursed by a care-taker with bodily touching. These qualitative observational results indicate that the new-born cynomolgus monkey can be used as a model of the human baby for research into the relationship between malnutrition and abnormal physical and mental growth.