Publisher Summary This chapter reviews the histopathologic, serologic, lymphocytic, virological, hormonal, and genetic characteristics of murine models of systemic lupus erythematosus (SLE). The pathogenetic mechanisms underlying murine SLE are highly complex, apparently well-programmed genetically, but still diverse and their bases not as yet well defined. Significant serologic and cellular experimental data support the statement that the final immunopathologic perturbation in murine (and human) SLE is a B lymphocyte hyperactivity with corresponding enhancement of serum antibodies and autoantibodies, particularly IgG, and consequent formation of pathogenic antigen–antibody ICs. On the basis of the available data, it appears that this B cell hyperactivity is polyclonal but not necessarily panclonal in nature, because not only antibodies against a wide array of autoantigens but also antibodies against incidental antigens, such as haptens, can be detected. The presence of autoantibodies and of their idiotypes in some recombinant lupus x normal murine lines expressing the normal partner's V genes, normal mice in which an exogenous or endogenous (Ipr gene) immunostimulator has been introduced, and unmanipulated normal mice indicate that lupus mice are not unique in their structural genetic Ig elements, whose presence determines the development of their autoimmune disease. The cause of B cell hyperactivity in lupus has not yet been fully elucidated. Autonomous B cell maturation does not appear likely, because B cell proliferation and differentiation in lupus mice was found to be dependent on the same number of accessory signals as in normal mice.

Murine models of systemic lupus erythematosus.

This 11th edition of the book Modern Nutrition in Health and Disease, featuring the work of more than 190 expert authors and divided into five parts, fully explains and encapsulates the fundamentals of nutrition and its role in contemporary society, from mastering the basic science of nutrient metabolism and function to applying nutritional concepts to combat human disease. Part I comprehensively covers specific dietary components, including major dietary constituents, minerals, vitamins and other Other CABI sites 

Modern Nutrition in Health and Disease

Publisher Summary This chapter discusses the formal genetics of mouse anemias and their significance for an analysis of patterns of mammalian gene action. It also describes normal hemopoietic development, homeostasis, and hemoglobin polymorphism. Anemias are classified into five categories—(1) anemias of maturation arrest, (2) anemias involving defects in iron utilization, (3) anemias involving greatly reduced erythrocyte life-span, (4) hemoglobinopathies, and (5) anemias almost secondary to genetically induced defects. During the total life of a mouse, including prenatal development, hemopoiesis takes place in four different sites. Although hemopoiesis continues in the liver until birth and for a brief time thereafter, hemopoiesis (largely myelopoiesis) commences in the spleen on fetal day 15 or 16 and in the marrow around the time of birth. Hematologically normal adult mice from many different inbred strains regularly produce more than one kind of hemoglobin. There is a widespread genetic polymorphism at both the Hba locus, determining the α-globin structure and the Hbb locus, determining the β-globin structure, and both the loci involve considerable genetic complexity.

Hereditary Anemias of the Mouse: A Review for Geneticists*

Publisher Summary This chapter discusses many observations indicating a decline in immune function with aging both in experimental animals and in humans. It is evident that a decline in T cell function gradually occurs and this affects the entire immune system. Antibody formation and B cell function appear to be secondarily altered. Various autoantibodies are increased in older experimental animals and humans that may relate to the observed decrease in suppressor cells. Cell-mediated immunity has been analyzed in vivo and in vitro. Various T cell-dependent functions decline with age. Normal immune functions can begin to decline as early as when an individual reaches sexual maturity. The decline is due to changes in the immune cells and their milieu. Cell loss, shift in the proportion of subpopulations, and qualitative cellular changes, the three possible types of changes that can cause the decline, have all been detected.

Age influence on the immune system.

Dietary restriction has been shown to have several health benefits including increased insulin sensitivity, stress resistance, reduced morbidity, and increased life span. The mechanism remains unknown, but the need for a long-term reduction in caloric intake to achieve these benefits has been assumed. We report that when C57BL/6 mice are maintained on an intermittent fasting (alternate-day fasting) dietary-restriction regimen their overall food intake is not decreased and their body weight is maintained. Nevertheless, intermittent fasting resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress. Intermittent fasting therefore has beneficial effects on glucose regulation and neuronal resistance to injury in these mice that are independent of caloric intake.

/pdf/intermittent-fasting-dissociates-beneficial-effects-of-42jlw4k25c.pdf

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Striking inhibition of development of renal disease and prolongation of lifespan have been achieved in kdkd mice by restricting their daily food intake. Restricting protein intake alone did not prolong life nor did it inhibit development of kidney disease. The kdkd nephronophthisis, although very different histologically from the renal disease of B/W mice, may also have immunological components. Like the immunologically based renal disease of B/W mice, renal disease in kdkd mice is decreased or eliminated histologically by dietary restriction, which inhibits development of autoimmunity directed toward the erythrocytes of these mice. Further analysis will be needed to elucidate the cause of progressive renal disease in both the kdkd and B/W models and to permit understanding of the profound influence of restriction of food intake on development and progression of these very different renal diseases.

Nutritional inhibition of genetically determined renal disease and autoimmunity with prolongation of life in kdkd mice

Summary1. Adult mice of the Z(C3H) strain have been made tolerant of skin homo-grafts of the(A X Z) F1 hybrid strain by repeated intravenous and intraperitoneal injections of homologous spleen cells. 2. Repeated intraperitoneal injections of homologous spleen cells generally failed to induce a tolerant state, although 3/75 recipients accepted the homologous skin homotransplant.

Tolerance of skin homografts induced in adult mice by multiple injections of homologous spleen cells.

Neonatally thymectomized C3H MTV+ (mammary tumor virus) female mice which were grafted with syngeneic thymus from either MTV+ or MTV- animals developed spontaneous mammary tumors as frequently as did sham-operated controls.

Neonatally thymectomized C3H MTV+ females which were injected with spleen cells obtained from syngeneic MTV+ mice had a significant reduction in mammary tumor incidence and a prolonged latent period of tumor development.

Neonatally thymectomized C3H MTV+ females which were injected with spleen cells obtained from syngeneic MTV- mice had a higher mammary tumor incidence and shorter latent period of tumor development than the neonatally thymectomized group treated with spleen cells obtained from syngeneic MTV+ mice.

These results suggest that, during early life, the thymus is critical for the normal development of spontaneous mammary carcinoma. We propose three possible mechanisms to explain the role of the thymus in spontaneous mammary carcinoma in mice: ( a ) The thymus may provide a necessary site for MTV latency and/or replication. ( b ) It could be that there are either endocrine functions of the thymus or endocrine interactions between the thymus and other organs which are not yet known. ( c ) The intact thymus is necessary for a “balanced” virus-host tumor cell immunologic interaction in a process of negative adaptation (tolerance) to the virus and/or virus-induced antigen(s). In this case, development of cancer may be a result of the tolerant state. Alternatively, cancer may develop as a result of breakdown of tolerance to the virus and/or virus-induced antigen(s). Our experiments seem to favor the latter explanation since our data suggest that host immune response (enhancing antibodies) or other immunologic reaction may contribute to the development and establishment of the cancer cells.

https://cancerres.aacrjournals.org/content/canres/29/1/174.full.pdf

Spontaneous Mammary Adenocarcinoma in Mice: Influence of Thymectomy and Reconstitution with Thymus Grafts or Spleen Cells

SummaryNZB mice are extensively used throughout the world as a model system for studying autoimmune disease. Apparently associated with a propensity to early development of autoimmune hemolytic anemia, the breeding capacity of NZB mice is defective; and the life span of these animals is short. As part of a general effort to improve breeding in our colonies, comparison of the influence of two commercial diets on NZB mice was made. One diet provided low protein and relatively high fat; the other, somewhat higher protein and lower fat content. Improved breeding performance was observed in the animals fed higher fat, lower protein intake. But, this diet influenced the animals adversely by fostering development of hemolytic anemia and shortening the life span both in males and females; whereas higher protein and lower fat extended particularly the longevity of male mice. These observations are taken as preliminary evidence that dietary intake can profoundly influence the development of autoimmune disease and t...

J. M. Smith

Papers

Nutritional inhibition of genetically determined renal disease and autoimmunity with prolongation of life in kdkd mice

Tolerance of skin homografts induced in adult mice by multiple injections of homologous spleen cells.

Spontaneous Mammary Adenocarcinoma in Mice: Influence of Thymectomy and Reconstitution with Thymus Grafts or Spleen Cells

Dietary Influence on Breeding Behavior, Hemolytic Anemia, and Longevity in NZB Mice

Spontaneous mammary adenocarinoma in mice: influence of thymectomy and reconstitution with thymus grafts or spleen cells