Polymorphisms of mouse apolipoprotein A-II: seven alleles found among 41 inbred strains of mice.

In mice, apolipoprotein A-II (apoA-II) associates to form amyloid fibrils in an age-associated manner. We determined the complete nucleotide sequences of the apoA-II gene (Apoa2) cDNA in 41 inbred strains of mice including Mus musculus domesticus (laboratory mouse), Mus musculus castaneus, Mus musculus molossinus, Mus musculus musculus and Mus spretus. Among these strains we identified 7 alleles (Apoa2a1, Apoa2a2, Apoa2b, Apoa2c, Apoa2d, Apoa2e and Apoa2f).

Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination.

Background: Fertility protection is an urgent clinical problem for prepubertal male oncology patients who undergo either chemotherapy or radiotherapy. As these patients do not have mature sperm to be frozen, there is as yet no effective method to preserve their fertility.

Methods And Results: Single pieces of immature mouse (1.

Induction of protein conformational change in mouse senile amyloidosis.

Aggregated amyloid fibrils can induce further polymerization of precursor proteins in vitro, thus providing a possible basis for propagation or transmission in the pathogenesis of amyloidoses. Previously, we postulated that the transmission of amyloid fibrils induces conformational changes of endogenous amyloid protein in mouse senile amyloidosis (Xing, Y., Nakamura, A.

Transmission of mouse senile amyloidosis.

In mouse senile amyloidosis, apolipoprotein A-II polymerizes into amyloid fibrils (AApoAII) and deposits systemically. Peripheral injection of AApoAII fibrils into young mice induces systemic amyloidosis (Higuchi et al, 1998). We isolated AApoAII amyloid fibrils from the livers of old R1.

Wild type ApoA-II gene does not rescue senescence-accelerated mouse (SAMP1) from short life span and accelerated mortality.

Biochemical and genetic data suggest that the Apoa2c allele of the apolipoprotein A-II gene causes severe senile amyloidosis (AApoAII) in SAMP1, a mouse model for accelerated senescence. We analyzed the effects of replacement of Apoa2c in SAMP1 mice with non-amyloidogenic Apoa2b on amyloidosis, lipoprotein metabolism, and progression of senescence using a congenic strain, P1.R1-Apoa2b, which has the Apoa2b chromosome region of SAMR1 in the genome of SAMP1.

Serum lipid concentrations and mean life span are modulated by dietary polyunsaturated fatty acids in the senescence-accelerated mouse.

The senescence-accelerated mouse (SAMP8) is an animal model used in studies of aging. This study was undertaken to investigate the effects of dietary PUFA on longevity (Experiment 1) and serum lipid concentrations (Experiment 2) in SAMP8 mice. Male mice were fed either an (n-3) PUFA-rich (9 g/100 g perilla oil) or an (n-6) PUFA-rich (9 g/100 g safflower oil) diet beginning at 6 wk of age.

Mouse senile amyloid deposition is suppressed by adenovirus-mediated overexpression of amyloid-resistant apolipoprotein A-II.

Apolipoprotein A-II (apoA-II), the second most abundant apolipoprotein of serum high density lipoprotein, deposits as an amyloid fibril (AApoAII) in old mice. Mouse strains with a high incidence of senile amyloidosis have the type C apoA-II gene (Apoa2(c)), whereas the strains with a low incidence of amyloidosis have the type B apoA-II gene (Apoa2(b)). In this study, to investigate whether the type B apoA-II protein inhibits the extension of amyloid fibrils, we constructed an adenovirus vector bearing the Apoa2(b) cDNA (Adex1CATApoa2(b)), which is expressed under the control of a hepatocyte-specific promoter.

Age-associated changes in elastin and collagen content and the proportion of types I and III collagen in the lungs of mice.

We investigated the effect of aging on the extracellular matrix of the lungs by examining age-associated changes in the elastin and collagen content, and the proportion of types I and III collagen, in the whole lungs of BALB/c and SAMR1 male mice between the ages of 3 and 24 months. The elastin content was determined by the hot alkali method. The hydroxyproline content was measured and assessed to be the collagen content.

Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase.

The alymphoplasia (aly) mutation of mouse is autosomal recessive and characterized by the systemic absence of lymph nodes (LN) and Peyer's patches (PP) and disorganized splenic and thymic structures with immunodeficiency. Although recent reports have shown that the interaction between lymphotoxin (LT) and the LT beta-receptor (Ltbeta r, encoded by Ltbr) provides a critical signal for LN genesis in mice, the aly locus on chromosome 11 is distinct from those for LT and its receptor. We found that the aly allele carries a point mutation causing an amino acid substitution in the carboxy-terminal interaction domain of Nf-kappa b-inducing kinase (Nik, encoded by the gene Nik).

Genetic typing of the senescence-accelerated mouse (SAM) strains with microsatellite markers.

The Senescence-Accelerated Mouse (SAM) strains constitute a murine model of accelerated senescence originating from the ancestral AKR/J strains and consist of nine senescence-prone (SAMP) strains and four senescence-resistant (SAMR) strains. The chromosomes (Chrs) of the SAM strains were typed with 581 microsatellite markers amplified by PCR, and the fundamental genetic information of the SAM strains was obtained. One-third of the examined markers displayed polymorphism among the strains, and only two alleles were detected in almost all loci among the SAM and AKR/J strains.

High-linoleate and high-alpha-linolenate diets affect learning ability and natural behavior in SAMR1 mice.

Semipurified diets incorporating either perilla oil [high in alpha-linolenate, 18:3(n-3)] or safflower oil [high in linoleate, 18:2(n-6)] were fed to senescence-resistant SAMR1 mouse dams and their pups. Male offspring at 15 mo were examined using behavioral tests. In the open field test, locomotor activity during a 5-min period was significantly higher in the safflower oil group than in the perilla oil group.

Identification of peak bone mass QTL in a spontaneously osteoporotic mouse strain.

The whole genome scan for quantitative trait loci (QTLs) specifying peak bone mass was performed with the F2 intercrosses of SAMP6, an established murine model of senile osteoporosis, exhibiting a significantly lower peak bone mass, and SAMP2, exhibiting a higher peak bone mass. Cortical thickness index (CTI), a parameter of bone mass of femurs, was measured in 488 F2 progeny at 4 months of age, when the animals attained peak bone mass by microphotodensitometry. Genetic markers were typed at 90 loci spanning all chromosomes except the Y.

Fibrilization in mouse senile amyloidosis is fibril conformation-dependent.

Amyloidosis refers to a group of diseases characterized by tissue deposition of amyloid fibrils. A single intravenous injection of a very small amount of the native mouse senile amyloid fibrils (AApoAII) induced severe systemic amyloid deposition in young mice having the amyloidogenic apoA-II gene (Apoa2c). After AApoAII injection, amyloid deposition occurred rapidly and advanced in an accelerated manner, as observed in spontaneous senile amyloidosis in mice.

Effects of proglumide on cholecystokinin-8-induced exocrine and endocrine pancreatic responses in conscious sheep.

The effects of cholecystokinin (CCK)-8, either alone or together with the CCK antagonist, proglumide on both exocrine and endocrine pancreatic responses were examined in conscious sheep. Intravenous infusions of CCK-8 (120 pmol/kg/min for 40 min) with vehicle (0 mumol/kg/min proglumide) significantly increased both amylase output in pancreatic juice and plasma insulin concentrations (P < 0.05).

Amyloid A protein amyloidosis induced in apolipoprotein-E-deficient mice.

Apolipoprotein E (apoE) is a constituent of lipoproteins other than low-density lipoprotein, and it principally acts in the transport and metabolism of plasma cholesterol and triglyceride. ApoE is a minor constituent of various kinds of amyloidoses and may play a role as a pathological chaperone for fibrillogenesis of amyloid fibril protein with the amyloid P component and proteoglycans. In this study, we examined the role of apoE in amyloidogenesis in vivo in apoE-deficient mutant mice with amyloid A protein (AA) amyloidosis induced by inflammatory stimulation.

Accumulation of pro-apolipoprotein A-II in mouse senile amyloid fibrils.

Apolipoprotein A-II (apoA-II), the major apoprotein of serum high-density lipoprotein, is deposited as amyloid fibrils (AApoAII) in murine senile amyloidosis. We have identified and purified a more basic amyloid protein from old-mouse liver. N-terminal sequencing of the protein revealed that the pro-segment of five amino acid residues (Ala-Leu-Val-Lys-Arg) extended from the N-terminal glutamine residue of mature apoA-II protein.

Regulation of the metabolism of plasma lipoproteins by apolipoprotein A-II.

Mouse apolipoprotein (apo) A-II has three variants (type A, B, and C) among inbred strains. To clarify the role of ApoA-II in the metabolism of high density lipoproteins (HDL), we constructed a new congenic mouse strain (P1.R1-Apoa2b) with type B ApoA-II of the SAMR1 strain on the genetic background of the SAMP1 strain, and examined it together with another ApoA-II congenic strain (R1.

Management and design of the maintenance of SAM mouse strains: an animal model for accelerated senescence and age-associated disorders.

The Senescence-Accelerated Mouse (SAM) was established by inbreeding and pedigree selection based on the life span, degree of senescence, as well as the incidence and degree of several age-associated disorders. At first, SAM strains were developed under conventional conditions, but now some strains are also maintained under specific pathogen-free conditions. There are many methods used to maintain such strains of mice; our methods will be introduced as one example of how to develop and maintain strains of mice used in aging research.

Accelerated senile amyloidosis induced by amyloidogenic Apoa-II gene shortens the life span of mice but does not accelerate the rate of senescence.

The SAMP1 strain is a mouse model for accelerated senescence and severe senile amyloidosis. We studied the effects of the amyloidogenic apolipoprotein A-II gene (Apoa2c) on senile amyloidosis and the life span and progress of senescence of congenic mice (R1.P1-Apoa2c) which have Apoa2c of the SAMPI strain on the genome of the normally aging SAMR1 strain.

Effects of intravenous infusions of cholecystokinin (CCK)-8 on exocrine and endocrine pancreatic secretion in conscious sheep.

The effects of cholecystokinin (CCK)-8 on both exocrine and endocrine pancreatic functions were examined simultaneously in five conscious sheep. Intravenous infusions of CCK-8 (0, 5, 10, 20, 30, 60, 120 and 240 pmol/kg/min for 40 min) induced dose-dependent increases in flow rate, and in protein and amylase outputs in pancreatic juice. The same CCK-8 infusions induced dose-dependent increases in plasma insulin, but no change in plasma glucagon concentrations.

Apolipoprotein A-II gene and development of amyloidosis and senescence in a congenic strain of mice carrying amyloidogenic ApoA-II.

Background: Apolipoprotein A-II (ApoA-II), a major apoprotein of serum high density lipoprotein (HDL) deposits as an amyloid fibril (AApoAII) in murine senile amyloidosis. Type C ApoA-II gene (Apoa2c) in the SAMP1 strain of mice, a murine model of severe senile amyloidosis and accelerated senescence was transferred on the genetic background of the SAMR1 strain, in which senile amyloidosis is rare and has a normal aging process, and a congenic strain of mouse (R1.P1-Apoa2c) was developed (Higuchi K, Kitado H, Kitagawa K, Kogishi K, Naiki H, Takeda T.

Development of congenic strains of mice carrying amyloidogenic apolipoprotein A-II (Apoa2c). Apoa2c reduces the plasma level and the size of high density lipoprotein.

A congenic strain of mice with amyloidogenic apolipoprotein A-II (Apoa2c) on the genetic background of the amyloidosis-resistant SAM-R/1 strain was produced by 12 generations of backcrossing. Genome mapping using endogenous murine leukemia proviral markers was done in the congenic strain, termed R1.P1-Apoa2c.

Developmental and age-related changes in apolipoprotein B mRNA editing in mice.

Apolipoprotein B (apoB) mRNA is modified by a post-transcriptional editing reaction (C to U) changing a glutamine (CAA) to a translational stop codon (UAA) and producing apoB-48 mRNA in mammalian liver and intestine. Developmental and age-related changes in apoB mRNA editing were studied using two mouse strains with different aging processes (SAM-R/1 with a normal aging process and SAM-P/1 with an accelerated aging process). During growth of both strains, the proportion of unedited (apoB-100) mRNA decreased from 80% in the fetal liver at the 17th day of gestation to 30% in the liver of mature 2-month-old mice.

Lung protein leakage in respiratory failure induced by a hybridoma making monoclonal antibody to the hydrophobic surfactant-associated polypeptide SP-B.

Adult mice were inoculated intraperitoneally with a hybridoma (8B5E) making monoclonal antibody to the porcine surfactant-associated polypeptide SP-B; this antibody cross-reacts with the corresponding polypeptide in the mouse surfactant system. Respiratory failure, developing 7-9 days after inoculation, was associated with a decrease in lung-thorax compliance determined during artificial ventilation, and an increase in the amount of protein including the specific antibody in lung lavage fluid. There was a statistically significant negative correlation between the compliance and the amount of protein as well as antibody recovered by lung lavage: r (log scale) = -0.

Semidominant expression of absence-like seizure in tremor rats.

Tremor rats (tremor homozygous rats) exhibit spontaneous absence-like seizure, which is characterized by a sudden immobility with staring and the appearance of 5- to 7-Hz spike and wave complexes in cortical and hippocampal electroencephalogram (EEG). In this study, we examined the development of the seizure and the mode of inheritance. All tremor homozygous and heterozygous rats exhibited the seizure by 14 and 26 weeks of age, respectively.