Identification and characterization of spontaneous AA amyloidosis in CD-1 mice used in toxicity studies: implications of SAA1 and SAA2 copy number variations.

Amyloidosis is characterized by the extracellular deposition of insoluble protein fibrils that cause cellular damage and dysfunction in organs and tissues. Multiple types of amyloidosis and their causative precursor proteins have been identified in humans and animals. In toxicological studies, a high incidence of spontaneous amyloidosis has been reported in CD-1 mice; however, the precursor protein responsible remains unclear.

Spontaneous B-cell lymphoma in the cranial mediastinal lymph node of an aged male C57BL/6J mouse.

B-cell lymphoma is generally observed in the spleen, mesenteric lymph nodes, and Peyer's patches in aged mice and rarely appears in other organs. Herein, we report a case of spontaneous B-cell lymphoma originating from the cranial mediastinal lymph node in a male 75-week-old C57BL/6J mouse. Macroscopically, a white mass was found at the base of the heart with no connection to the thymus.

PMEL p.L18del associates with beef quality of Kumamoto sub-breed of Japanese Brown cattle.

Japanese Brown cattle is the second most popular breed among Wagyu breeds and raised mainly in Kumamoto and Kochi Prefectures. Typical coat color of the Kumamoto sub-breed is solid brown, but individuals with diluted coat color are sometimes born. We previously detected four SNPs in PMEL gene and identified p.

Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats.

In drug development, assessment of non-clinical peripheral neurotoxicity is important to ensure human safety. Clarifying the pathological features and mechanisms of toxicity enables the management of safety risks in humans by estimating the degree of risk and proposing monitoring strategies. Published guidelines for peripheral neurotoxicity assessment do not provide detailed information on which endpoints should be monitored preferentially and how the results should be integrated and discussed.

Causative alleles for chondrodysplastic dwarfism, factor XI deficiency, and factor XIII deficiency in the Kumamoto sub-breed of Japanese Brown cattle.

Japanese Brown cattle are the second most popular Wagyu breed, and the Kumamoto sub-breed shows better daily gain and carcass weight. One of the breeding objectives for this sub-breed is to reduce genetic defects. Chondrodysplastic dwarfism and factor VIII deficiency have been identified as genetic diseases in the Kumamoto sub-breed.

Evolutionary activation of acidic chitinase in herbivores through the H128R mutation in ruminant livestock.

Placental mammals' ancestors were insectivores, suggesting that modern mammals may have inherited the ability to digest insects. Acidic chitinase (Chia) is a crucial enzyme hydrolyzing significant component of insects' exoskeleton in many species. On the other hand, herbivorous animal groups, such as cattle, have extremely low chitinase activity compared to omnivorous species, e.

PMEL p.Leu18del dilutes coat color of Kumamoto sub-breed of Japanese Brown cattle.

Background: Coat color is important for registration and maintenance of livestock. Standard coat color of Kumamoto sub-breed of Japanese Brown cattle is solid brown, but individuals with diluted coat color have been observed recently. In this study, we attempted to identify polymorphism(s) responsible for coat color dilution by whole genome analysis.

Leptin gene contributes to beef marbling standard, meat brightness, meat firmness, and beef fat standard of the Kumamoto sub-breed of Japanese Brown cattle.

The Kumamoto sub-breed of Japanese Brown cattle has unique characteristics, such as great growth rate, and their contribution as future breeding materials is expected. To develop a DNA marker for their breeding, we investigated the effects of Leptin gene, controlling energy homeostasis, on carcass traits of the Kumamoto sub-breed. Sequence comparison identified five single nucleotide polymorphisms (SNPs): four linked synonymous mutations and one nonsynonymous mutation.

Noninsect-Based Diet Leads to Structural and Functional Changes of Acidic Chitinase in Carnivora.

Acidic chitinase (Chia) digests the chitin of insects in the omnivorous stomach and the chitinase activity in carnivorous Chia is significantly lower than that of the omnivorous enzyme. However, mechanistic and evolutionary insights into the functional changes in Chia remain unclear. Here we show that a noninsect-based diet has caused structural and functional changes in Chia during the course of evolution in Carnivora.

Karnovsky's fixative prevents artifacts appearing as vacuolation derived from tissue processing in kidneys treated with antisense oligonucleotide.

Antisense oligonucleotide (ASO) therapies have been identified as a new treatment modality for intractable diseases. In kidneys treated with ASOs, vacuoles, in addition to basophilic granules, are often observed in the proximal tubules. Some reports have described that these vacuoles are likely to be a secondary phenomenon resulting from the extraction of ASOs during tissue processing.

Spontaneous ovarian choriocarcinoma in a young ICR mouse.

This paper describes the spontaneous ovarian choriocarcinoma observed in a young female Crl:CD1 (ICR) mouse. The mouse was sacrificed at 8 weeks of age after oral administration of a compound for 2 weeks. The left ovary was found to be cystically enlarged with dark red hemorrhaging.

Metabolomic profiling of urine-derived extracellular vesicles from rat model of drug-induced acute kidney injury.

Extracellular vesicles (EVs) are lipid bilayer particles that are released by various cells and provide a real-time snapshot of the state of these cells in tissue in a noninvasive manner. EVs contain components, including mRNA, miRNAs, proteins, and metabolites. Therefore, EVs hold promise for the discovery of liquid biopsy-based biomarkers for disease diagnosis.

Underground locomotion in moles: kinematic and electromyographic studies of locomotion in the Japanese mole (Mogera wogura).

A series of kinematic and electromyographic (EMG) studies were conducted to characterize the neural control of underground movement in the Japanese mole, Mogera wogura. For the purposes of the present study, the locomotion of moles was classified into two modes: crawling, which comprises alternate movements of the left and right forelimbs; and burrowing, in which both forelimbs move synchronously. In crawling, moles exhibit both symmetrical and asymmetrical locomotion independent of cycle duration and speed of travel.

Spontaneous hyaline glomerulopathy in a young Slc:ICR mouse.

Hyaline glomerulopathy is a type of glomerular lesion that occurs in aging mice. Spontaneous hyaline glomerulopathy is rare in young mice. Here, we report spontaneous hyaline glomerulopathy in a young adult (15-week-old) ICR mouse.

Tethered spinal cord related to caudal spinal dysraphism in a tailless Holstein calf.

A rare dysraphic caudal spinal anomaly, or caudal agenesis, comprising a tethered spinal cord, was found in a tailless Holstein calf that presented ataxia and paresis with analgesia of the hind limbs. The gently and slimly tapered conus medullaris was poorly formed between S2 and S3 which indicated that it was lying more caudally. The caudal end of the filum terminale adhered to the inner periosteum of the vertebral arch at S4, which is compatible with tethering of the spinal cord.

Dual phosphorylation of protein phosphatase PPM1H promotes dephosphorylation of Smad1 in cellulo.

Protein phosphatase PPM1H is known to participate in various biological or pathophysiological mechanisms. However, little is known about the molecular mechanisms of its regulation. In this study, we investigated the protein kinases that directly phosphorylate PPM1H, identifying them as cAMP-dependent protein kinase (PKA) and Ca/calmodulin-dependent protein kinase I (CaMKI).

MC1R c.310G>- and c.871G > A determine the coat color of Kumamoto sub-breed of Japanese Brown cattle.

Coat color is one of the important factors characterizing breeds for domestic animals. Melanocortin 1 receptor (MC1R) is a representative responsible gene for this phenotype. Two single-nucleotide polymorphisms (SNPs) in bovine MC1R gene, c.

Residues of acidic chitinase cause chitinolytic activity degrading chitosan in porcine pepsin preparations.

Commercially available porcine pepsin preparations have been used for the production of chitooligosaccharides with various biomedical activities. However, the origin of this activity is not well understood. Here we show that the chitosan-degrading activity is conferred by residues with chitinolytic activity of truncated forms of acidic chitinase (Chia) persisting in the pepsin preparation.

The variable heartbeat of Japanese moles (Mogera spp.).

This report demonstrates the variable cardiac rhythm in two species of subterranean mole, the large Japanese mole (Mogera wogura) and the lesser Japanese mole (Mogera imaizumii). The phenomenon was revealed using X-ray videos of M. wogura and investigated in detail using electrocardiogram (ECG) traces recorded with implanted electrodes in this species and M.

High expression of acidic chitinase and chitin digestibility in the stomach of common marmoset (Callithrix jacchus), an insectivorous nonhuman primate.

Chitin is a polymer of N-acetyl-D-glucosamine (GlcNAc) and a main constituent of insects' exoskeleton. Insects are rich in protein with high energy conversion efficiency. Recently, we have reported that acidic chitinases (Chia) act as digestive enzymes in mouse, pig and chicken (omnivorous) but not in dog (carnivorous) and bovine (herbivorous), indicating that feeding behavior affects Chia expression levels, and determines chitin digestibility in the particular animals.

Imaging mass spectrometry for toxicity assessment: a useful technique to confirm drug distribution in histologically confirmed lesions.

To evaluate the usefulness of imaging mass spectrometry (IMS) technology for assessing drug toxicity, we analyzed animal tissues in an amiodarone (AMD)-induced phospholipidosis model by IMS and confirmed the relationship between the distribution of AMD, its metabolites, and representative phospholipids (phosphatidylcholine, PC) and histological changes. AMD was administered to rats for 7 days at 150 mg/kg/day. The lung, spleen, and mesenteric lymph node were histologically examined and analyzed using IMS.

Acidic Chitinase-Chitin Complex Is Dissociated in a Competitive Manner by Acetic Acid: Purification of Natural Enzyme for Supplementation Purposes.

Acidic chitinase (Chia) has been implicated in asthma, allergic inflammations, and food processing. We have purified Chia enzymes with striking acid stability and protease resistance from chicken and pig stomach tissues using a chitin column and 8 M urea (urea-Chia). Here, we report that acetic acid is a suitable agent for native Chia purification from the stomach tissues using a chitin column (acetic acid-Chia).

Chitin digestibility is dependent on feeding behaviors, which determine acidic chitinase mRNA levels in mammalian and poultry stomachs.

Chitin, a polymer of N-acetyl-D-glucosamine (GlcNAc), functions as a major structural component in chitin-containing organism including crustaceans, insects and fungi. Recently, we reported that acidic chitinase (Chia) is highly expressed in mouse, chicken and pig stomach tissues and that it can digest chitin in the respective gastrointestinal tracts (GIT). In this study, we focus on major livestock and domestic animals and show that the levels of Chia mRNA in their stomach tissues are governed by the feeding behavior.

Mouse acidic mammalian chitinase exhibits transglycosylation activity at somatic tissue pH.

Mouse acidic mammalian chitinase (AMCase) degrades chitin with highest efficiency at pH 2.0 and is active up to pH 8.0.