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Biomedical subjects

J H Tjio

Publications and source records attributed to J H Tjio.

At least 37 records · Page 2Linked to original sources

Genetic studies in NZB mice. I. Spontaneous autoantibody production.

The appearance of naturally occurring thymocytotoxic autoantibodies (NTA) and spontaneously produced antibodies to single-stranded DNA (ssDNA) was studied in NZB, and DBA/2 mice and their F1 and backcross progeny. NTA production was markedly decreased in males; however, castrated males produced quantities of NTA similar to those of females. Because the amount of NTA was influenced by sex hormones, it was necessary to gonadectomize all progeny to determine the mode of inheritance. Such studies suggested that NTA production was determined by a single locus with a gene dosage (codominant) mode of expression. The spontaneous production of antibodies to ssDNA appeared to be inherited as a single dominant genetic trait. The quantity of anti-ssDNA was also found to be under additional regulation; either a gene dosage effect or more likely a regulatory gene. The genes controlling the presence and quantity of ssDNA antibodies were not linked to the gene controlling the appearance of NTA.

Alleles↗

Marrow regeneration after mechanical depletion.

The origin of marrow regeneration after mechanical depletion was reinvestigated in mouse chimeras. The results were compatible with the local origin of stem cells from remnants of incompletely removed marrow, but not with their origin from a common precursor of both bone and hemopoietic cell lines. In transplanted femurs depleted by a modified technique of in vivo evacuation of marrow, hemopoietic regeneration failed to occur. The presence of hemopoietic stem cells in the Haversian canals was thus excluded. The demonstration of ample hemopoiesis with minimal bone formation in nondepleted controls in which bone marrow initially became necrotic provided new evidence that osteogenesis was not a prerequisite of hemopoietic regeneration.

Animals↗

Hematopoietic differentiative properties of murine spleen implanted in the omenta of irradiated and nonirradiated hosts.

Whole body irradiation of the recipients of syngeneic splenic implants into the omentum greatly enchances hematopoiesis and permits survial of and repopulation by stem cells of donor origin. Donor hematopioetic stem cells do not survive in spleen implants of the nonirradiated host; irradiated hosts were therfore used in the bulk of the experiments. Differentiation in the implants of splenic fragments is predominantly erythrocytic at 10 days and shifts to predominantly granulocytic differentiation at 21 days. Suspensions of spleen cells injected into the ometntum are predominantly granulocytopioetic at 10 days. The differntiation in fragments of spleen depleted of stem cells by irradtion, seeded with bone marrow cells and implanted into the omentum results in mixed erythocytic and granulocytic hematopoiesis, with granulocytic predominance. Lymphocytic cells appeared late in the implants of irrdiated recipients even at a time of prolific lymphocytopoiesis in the host's own spleens. The cause of the delay in the implants is not clear. The data are consisent with the concept that differntiation of hematopioetic stem cells is influenced by the stromal cells of the parent organ. The erythrocytic inductive capacity of the stromal cells may be lost by mechanical disruption or modified by irraidation or a prolonged period of implantation.

Animals↗

Studies of mice with a balanced complement of 36 chromosomes derived from F 1 hybrids of T1Wh and T1Ald translocation homozygotes.

F(1) hybrids with 38 chromosomes, including single T1Wh and T1Ald translocations, resulted when mice homozygous for the Robertsonian translocations T1Wh and T1Ald were crossed. Meiotic studies of the hybrids showed two trivalents, indicating nonhomology of the T1Wh and T1Ald chromosomes. The hybrids had frequent (25%) unbalanced meiotic metaphase II complements; one trisomic mouse resulted from six F(1) crosses. The F(1) crosses also produced one mouse with 36 chromosomes homozygous for both T1Wh and T1Ald, as well as mice with balanced polymorphic complements of 37, 38, 39, and 40 chromosomes. By crossing the F(2), a homogeneous line with 36 chromosomes was established. The line is phenotypically normal, fertile, and has balanced meiotic metaphase II complements. Analysis of the chromosomes of these mice with quinacrine mustard and the Giemsa-banding technique confirmed that T1Wh and T1Ald consisted of chromosomes 5;19 and 6;15, respectively. Crosses between this line and other existing translocation stocks may produce new strains of mice with even further reduction in chromosome number. Accumulation of Robertsonian translocations, a possible evolutionary mechanism in the wild, can be studied in the laboratory. F(1) hybrids from certain crosses are also an important model for human translocation carriers; both have similar meiotic abnormalities and often have aneuploid offspring.

Aneuploidy↗