Biomedical subjects
Publications and source records attributed to C T Hansen.
The motheaten mouse is an immunodeficient mutant which has been found to have elevated immunoglobulin levels, to exhibit autoimmunity, and early death. Since survival is not improved by a germfree environment, it appears that some mechanism other than infection results in its early demise.
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C-type virus particles were observed by electron microscopy in cultures of a cell line (NML-1) derived from a lymphosarcoma that arose spontaneously in a nude NIH outbred mouse. The presence of such particles indicated that human tumors heterotransplanted in nude mice might become contaminated with murine oncornaviruses.
A radiation-induced autosomal recessive mutant in the rat called vibrissaeless (vb), has been described and studied. Mutants have abnormal hair growth, the hairs being reduced in number and length. Mutant animals form blisters which then erode, crust, and heal without scars. The blisters can be artificially produced by friction and result from intraepidermal separation which is suprabasilar in position. To date, we cannot correlate this abnormality in rats with any known inherited human blistering disease.
Serum IgM immunoglobulin levels and antibody responses to an optimally immunogenic dose of Type III pneumococcal polysaccharide (SSS-III) were assessed for F(1), F(2), and backcross progeny derived from crosses between high responding BALB/cAnN (B) and low responding CBA/HN (C) mice. The results obtained confirmed our original hypothesis, namely, that a major component, present on the X chromosome, governs the ability to respond to SSS-III in a decisive manner. Although all low responding C mice had low IgM levels, both intermediate and high responders had high IgM levels of the same magnitude. Treatment with bacterial lipopolysaccharides (LPS) resulted in a significant increase in the IgM levels of low responding C mice. While the IgM levels attained were similar to those of high responding B mice, not given LPS, no antibody specific for LPS appeared to be produced. These findings suggest that C mice are unable to make an IgM antibody response to SSS-III and other polysaccharide antigens, despite the fact that they possess the capacity to synthesize normal amounts of IgM immunoglobulin.
The IgM antibody response to Type III pneumococcal polysaccharide (SSS-III) was assessed in F(1), F(2), and backcross progeny derived from high (BALB/cAnN) and extremely low (CBA/HN) responding parental strains of inbred mice. The results of these studies indicated that a major component involved in the antibody response is X-linked, i.e., carried on the X chromosome; this component determines responsiveness to SSS-III in an almost quantal or "all-or-none" manner. Other factors, presumably autosomal genes, regulate the magnitude of the antibody response produced by mice possessing the X-linked gene; these appear to influence independently the number of antibody-producing cells found after immunization and the amount of antibody made by such cells. Strains of inbred mice varied widely in their ability to respond to SSS-III. Responsiveness was not associated with H-2 histocompatibility type. The implications of these findings with respect to the genetic control of the antibody response to SSS-III are discussed.
The lipid changes in the inheritable foam cell reticulosis of mice discovered by Lyons, Hulse, and Rowe have been reexamined. The major abnormality in thymuses from homozygous-abnormal animals has been identified as an increase in the concentration (per milligram of protein) of sphingomyelin and cholesterol. This increase is associated with normal sphingomyelin-cleaving activity. The lipid compositions of the liver and spleen in the homozygous-abnormal animal and of the thymus in the heterozygous-abnormal mouse are normal. The disorder appears to be chemically analogous to those forms of human sphingomyelin lipidosis (Niemann-Pick disease) that are not accompanied by a decrease in tissue sphingomyelinase.
An autosomal recessive mutation had been previously X-ray-induced in the rat and named the masked rat (genotype mk/mk). This study describes the mutant's appearance, histology, and microflora. The rat's eyelids were swollen, often to the point of closure, and its face was partially covered by a brownish crust, giving the mutant a mask-like appearance. The chronic blepharitis was also accompanied by alopecia that appeared as bare patches across the mutant's back. Pasteurella pneumotropica was found in eyelids and on skin from all masked rats. The normal rat demonstrated a resistance to Pasteurella pneumotropica infection, or, conversely, the masked rat appeared to be genetically predisposed to pasteurellosis.
The heart and aorta weights in 23 strains of rats and the four-way cross generation among the M520/N, SHRSP/N, SHR/N, and WKY/N strains were investigated in relation to their blood pressure in an attempt to characterize cardiovascular enlargement (increased weight of heart and aorta) from a genetic aspect. The distribution of blood pressure in these strains at 10 weeks of age was clearly divided into hypertensive and normotensive groups. In the hypertensive group, heart weight increased in proportion to blood pressure. In contrast, there was no relationship between blood pressure and heart weight in the normotensive group in spite of large strain differences in heart weights. The result of variance analysis exhibited a significant strain difference in heart weight, and the degree of genetic determination was estimated to be 65%-75%. A similar genetic influence was apparent for normotensive strains excluding hypertensive strains. The distribution of blood pressures in the four-way cross generation showed the segregation of three phenotypes consisting of normotensive, intermediate and hypertensive groups. A large variability was seen in heart weight of each group. However, the increase in average heart weight of these three groups was very small. The degree of genetic determination from the cross analysis was estimated to be 45%-65%. These results indicate that heart weight is a highly heritable trait, and that the effect of genetic factors on cardiac enlargement is larger than that of blood pressure. A similar result was obtained for the aorta weight. However, the effect of genetic factors was less important for aorta weight than for heart weight since the degree of genetic determination was estimated to be 45%-65% from the strain comparison and 35%-60% from the cross analysis.
Enlargement and nucleic acid content of the cardiovascular system of several strains (SHRSP/N, SHR/N, OM/N, M520/N) of rats were compared with the WKY/N strain in an attempt to characterize cardiac enlargement. Cardiac enlargement in rats can be due to either hypertrophy (increase in myocyte size), hyperplasia (increase in cell number including supporting tissue), or a combination of both. The sum of the indices of the degree of hypertrophy and hyperplasia calculated from the difference of the heart and aorta deoxyribonucleic acid (DNA) concentration and total DNA content between each strain and the WKY/N was almost equal to the degree of heart and aorta enlargement. The SHRSP/N revealed a striking hypertrophy of myocardial cells from the prehypertensive stage, and hyperplasia appeared gradually with the elevation of blood pressure. In contrast, the SHR/N developed a marked hyperplasia with some hypertrophy at the prehypertensive stage. Cardiac enlargement of the OM/N was attributed to both hypertrophy and hyperplasia. A large heart weight of the M520/N was recognized at only a young age, and was due almost entirely to hyperplasia. Aortic enlargements were related to hyperplasia. An increased ribonucleic acid (RNA) concentration was observed in both ventricles of the SHRSP/N, SHR/N, and M520/N rats at 4 weeks of age, and in all of the four strains at 16 weeks of age. A significantly higher RNA concentration was indicated in the aorta of three hypertensive strains of SHRSP/N, SHR/N, and OM/N at established hypertensive stage. These changes might be related to manifestations of genetic or other factors such as the effect of elevated blood pressure.
The Spontaneous Hypertensive/NIH-corpulent rat is a recently developed genetic model of obesity and diabetes. The strain exhibits both metabolic and histopathological characteristics associated with non-insulin dependent diabetes mellitus in humans. This rodent model is unique in that glucose intolerance is expressed in both sexes and in both phenotypes.