Insulin resistance, steatohepatitis, and hepatocellular carcinoma in a new congenic strain of Fatty Liver Shionogi (FLS) mice with the Lep(ob) gene.

In order to examine the influence of obesity on metabolic disorder and liver pathogenesis of the Fatty Liver Shionogi (FLS) mouse, which develops hereditary fatty liver and spontaneous liver tumors, we established a new congenic strain named FLS-Lep(ob). The Lep(ob) gene of the C57BL/6JWakShi (B6)-Lep(ob)/Lep(ob) mouse was transferred into the genome of the FLS mouse, by backcross mating. FLS-Lep(ob)/Lep(ob) mice were maintained by intercrossing between Lep(ob)-heterozygous littermates.

Natural dental caries in molars of osteogenic disorder Shionogi rats.

Osteogenic disorder Shionogi (ODS) rats are genetically defective in ascorbic acid biosynthesis. They exhibit a gait abnormality due to dysfunctional bone formation and display various dental abnormalities. Conditions of the oral cavity and tooth quality both influence the development of dental caries.

MHC-linked susceptibility to type 1 diabetes in the NOD mouse: further localization of Idd16 by subcongenic analysis.

Although major histocompatibility complex (MHC)-linked susceptibility is the strongest component, recent studies demonstrated that MHC-linked susceptibility to type 1 diabetes consists of multiple components both in humans and non-obese diabetic (NOD) mouse. In the NOD mouse, Idd16 has been mapped to the region adjacent to, but distinct from Idd1 in the MHC class II region. Establishment of subcongenic NOD.

Contribution of class III MHC to susceptibility to type 1 diabetes in the NOD mouse.

A recombinant major histocompatibility complex (MHC) with the same class III region as the NOD mouse, but different class II region from the NOD mouse was identified in the NON mouse, and NOD mice congenic for this recombinant MHC, NOD.NON-H2, was established. None of the congenic mice homozygous for the NON MHC developed type 1 diabetes, indicating that the NOD MHC is necessary for the development of type 1 diabetes.

High sensitivity of fatty liver Shionogi (FLS) mice to diethylnitrosamine hepatocarcinogenesis: comparison to C3H and C57 mice.

The fatty liver Shionogi (FLS) mouse is a new inbred strain that spontaneously develops fatty liver with infiltration of mononuclear cells. Moreover, this mouse is known to frequently develop spontaneous hepatic cancers. Recently, human non-alcholic steatohepatitis (NASH) has been focused of attention regarding hepatocellular carcinoma.

Differences in susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis between SD/gShi rats with spontaneous hypospermatogenesis and SD/cShi rats with spontaneous hydronephrosis.

Differences in susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis between two substrains of male Sprague-Dawley rats were examined. One substrain was SD/gShi, which has spontaneous hypospermatogenesis, and the other was SD/cShi, which is a sister strain of SD/gShi, and has normal testis but spontaneous hydronephrosis. SD/gShi rats had a lower incidence of urinary bladder tumors and had lower 5-bromo-2'-deoxyuridine labeling indices in the urinary bladder epithelium than SD/cShi rats when BBN was given.

Evidence for Cd101 but not Fcgr1 as candidate for type 1 diabetes locus, Idd10.

Among polygenes conferring susceptibility to type 1 diabetes in the NOD mouse, Idd10 on distal chromosome 3 has been shown to be important for disease susceptibility. In this study, we investigated the candidacy of Fcgr1 and Cd101 for Idd10, by congenic mapping and candidate gene sequencing. Among seven NOD-related strains studied, the IIS mouse was found to possess a recombinant Idd10 interval with the same sequence at Fcgr1 as the NOD mouse, but a different sequence at Cd101 from that in the NOD mouse with 10 amino acid substitutions.

Idd1 and Idd3 are necessary but not sufficient for development of type 1 diabetes in NOD mouse.

Type 1 diabetes in the NOD mouse is under polygenic control, with a major susceptibility gene, Idd1, in the major histocompatibility complex (MHC). To investigate the contribution of the NOD MHC to type 1 diabetes susceptibility, a B6.NOD-H-2 congenic strain, in which the NOD MHC was introgressed onto the genetic background of the C57BL/6 strain, was established.

Congenic mapping and candidate sequencing of susceptibility genes for Type 1 diabetes in the NOD mouse.

Inheritance of type 1 diabetes is polygenic with a major susceptibility gene located in the major histocompatibility complex (MHC). In addition to MHC-linked susceptibility, a number of susceptibility genes have been mapped outside the MHC in both humans and animal models. In order to localize and identify susceptibility genes for type 1 diabetes, we have developed a series of congenic strains in which either susceptibility intervals from the NOD mouse, a mouse model of type 1 diabetes, were introgressed onto control background genes or protective intervals from control strains were introgressed onto NOD background genes.

Role of the Nh (Non-hair) mutation in the development of dermatitis and hyperproduction of IgE in DS-Nh mice.

The DS-Nh (DS Non-hair) mouse is a spontaneous hairless mutant of the DS mouse. The inheritance mode of the Nh mutation is autosomal dominant, and the Nh locus is mapped to Chromosome 11. The roles of the Nh mutation in spontaneous dermatitis and IgE hyperproduction were studied using an Nh congenic strain with a genetic background from the BALB/c mouse.

Spontaneous development of hepatocellular carcinomas in the FLS mice with hereditary fatty liver.

The fatty liver Shionogi (FLS) mouse is an inbred strain that develops spontaneous fatty liver (hepatic steatosis) chronically without obesity. Here, we reported that the mice develop spontaneous hepatocellular tumors with high incidences. The mice with age of over 1 year frequently developed whitish protuberant nodules in the livers, which were histologically diagnosed as hepatocellular adenoma and/or carcinoma (HCC).

Spontaneous development of dermatitis in DS-Nh mice under specific pathogen-free conditions.

Spontaneous development of dermatitis in DS-Nh mice under specific pathogen-free conditions was examined to verify the hypothesis [Exp. Anim. 46: 225-229, 1997] that Stapylococcus aureus (S.

Changes in catecholamine metabolism by ascorbic acid deficiency in spontaneously hypertensive rats unable to synthesize ascorbic acid.

We have previously reported the establishment of a novel rat strain, SHR-od, with both spontaneous hypertension and a defect of ascorbic acid biosynthesis. Blood pressure in mature SHR-od fed an ascorbic acid-supplemented diet is over 190-200 mmHg, while it decreased to around 120 mmHg at 4-5 weeks after the cessation of ascorbic acid supplementation. With regard to possible mechanisms of blood pressure lowering, we focused on catecholamine synthesis in adrenal glands, since catecholamine is a major factor for blood pressure regulation and ascorbic acid is a co-factor of dopamine beta-hydroxylase (DBH) in catecholamine biosynthesis.

Ob/ob mice as a model of delayed gastric emptying.

Diabetic gastroparesis is a well-recognized delay of gastric emptying in diabetic patients. We assessed the gastric emptying rate in ob/ob mice, a genetic model of obesity and diabetes. The basal gastric emptying rate in 22- to 27-week-old ob/ob mice was significantly lower than that in 10- to 11-week-old ob/ob mice (P<.

Impaired urinary concentrating ability in genetically polyuric mice.

Newly recognized strain of mice with hereditary polyuria (PUS mice) was characterized. Polyuria was inherited as a single autosomal-recessive trait. At 15 weeks, PUS mice excreted hypotonic (urine osmolality: PUS;270.

Induction of tumors in the colon and liver of the immunodeficient (SCID) mouse by 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ)-modulation by long-chain fatty acids.

We have recently shown that immunodeficient (SCID) mice, which lack functional T and B cells, are highly susceptible to low dose site specific induction of colon aberrant crypt foci (ACF), surrogates for colon tumors, by 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ). To test whether long-term exposure to a high dose in the diet might prove carcinogenic to the SCID mouse colon, in contrast to other mice strains tested to date, the compound was administered at 300 p.p.

Genetic dissection of type 1 diabetes susceptibility gene, Idd3, by ancestral haplotype congenic mapping.

One of the strongest non-MHC susceptibility genes for type 1 diabetes, Idd3, has been mapped to a 0.15-cM segment of chromosome 3, where a strong candidate gene, Il2, encoding cytokine IL2, is located. To prove that the NOD allele of Il2 is responsible for the Idd3 effect, it is necessary to find a recombinant chromosome with the NOD allele of Il2, but with different flanking markers from NOD mice, and to demonstrate that NOD mouse strains that are congenic for the recombinant Il2 region develop type 1 diabetes with similar incidence and age at onset of the disease.

Sequence analysis of Tnf as a candidate for Idd16.

Linkage analysis and congenic mapping have localized 18 loci (Idd1-18) that contribute to the development of autoimmune type 1 diabetes in the nonobese diabetic (NOD) mouse. By using a congenic NOD strain which possesses recombinant MHC from a closely related CTS strain, a susceptible region (Idd16) was mapped to the segment adjacent to, but distinct from class II A and E genes (Idd1). The tumor necrosis factor alpha gene (Tnf), which is located within the Idd16 region, has been suspected to be a candidate gene for type 1 diabetes in the NOD mouse.