Dominant effect of a single amino acid mutation in the motor domain of myosin VI on hearing in mice.

An unconventional myosin, myosin VI gene (MYO6), contributes to recessive and dominant hearing loss in humans and mice. The Kumamoto shaker/waltzer (ksv) mouse is a model of deafness resulting from a splice-site mutation in Myo6. While ksv/ksv homozygous mice are deaf due to cochlear hair cell stereocilia fusion at the neonatal stage, the hearing phenotypes of ksv/+ heterozygous mice have been less clear.

Mouse NOD/Shi and NSY/Hos strains infected with Plasmodium berghei ANKA are models for experimental cerebral malaria.

In humans, cerebral malaria is the most common cause of malaria-related mortality. Mouse C57BL/6 (B6) sub-strains are the major model system for experimental cerebral malaria (ECM) as they show similar pathophysiology to human cerebral malaria after infection with the rodent malaria parasite Plasmodium berghei ANKA. This model system has been used to analyze the molecular mechanisms of cerebral malaria.

Muscle-specific lack of Gfpt1 triggers ER stress to alleviate misfolded protein accumulation.

Pathogenic variants in GFPT1, encoding a key enzyme to synthesize UDP-N-acetylglucosamine (UDP-GlcNAc), cause congenital myasthenic syndrome (CMS). We made a knock-in (KI) mouse model carrying a frameshift variant in Gfpt1 exon 9, simulating that found in a patient with CMS. As Gfpt1 exon 9 is exclusively expressed in striated muscles, Gfpt1-KI mice were deficient for Gfpt1 only in skeletal muscles.

Structural basis for the recognition of α-1,6-branched α-glucan by GH13_47 α-amylase from Rhodothermus marinus.

Glycoside hydrolase (GH) family 13 is among the main families of enzymes acting on starch; recently, subfamily 47 of GH13 (GH13_47) has been established. The crystal structure and function of a GH13_47 enzyme from Bacteroides ovatus has only been reported to date. This enzyme has α-amylase activity, while the GH13_47 enzymes comprise approximately 800-900 amino acid residues which are almost double those of typical α-amylases.

Calcitriol ameliorates motor deficits and prolongs survival of Chrne-deficient mouse, a model for congenital myasthenic syndrome, by inducing Rspo2.

Signal transduction at the neuromuscular junction (NMJ) is compromised in a diverse array of diseases including congenital myasthenic syndromes (CMS). Germline mutations in CHRNE encoding the acetylcholine receptor (AChR) ε subunit are the most common cause of CMS. An active form of vitamin D, calcitriol, binds to vitamin D receptor (VDR) and regulates gene expressions.

C3H/HeNSlc mouse with low phospholipid transfer protein expression showed dyslipidemia.

High serum levels of triglycerides (TG) and low levels of high-density lipoprotein cholesterol (HDL-C) increase the risk of coronary heart disease in humans. Herein, we first reported that the C3H/HeNSlc (C3H-S) mouse, a C3H/HeN-derived substrain, is a novel model for dyslipidemia. C3H-S showed hypertriglyceridemia and low total cholesterol (TC), HDL-C, and phospholipid (PL) concentrations.

Characterization and alteration of product specificity of Beijerinckia indica subsp. indica β-fructosyltransferase.

The trisaccharide 1-kestose, a major constituent of fructooligosaccharide, has strong prebiotic effects. We used high-performance liquid chromatography and 1H nuclear magnetic resonance spectroscopy to show that BiBftA, a β-fructosyltransferase belonging to glycoside hydrolase family 68, from Beijerinckia indica subsp. indica catalyzes transfructosylation of sucrose to produce mostly 1-kestose and levan polysaccharides.

Neonatal lethality of mouse A/J-7 consomic strain is caused by an insertion mutation in the Dchs1 gene.

Homosomic mice of the A/J-7 consomic mouse strain that introduced the entire chromosome 7 (Chr 7) of SM/J into the A/J strain exhibited neonatal lethality. We tentatively maintained segregating inbred strains (A/J-7A and A/J-7D) in which the central portion of Chr 7 was heterozygous for the A/J and SM/J strains, and the centromeric and telomeric sides of Chr 7 were homozygous for the SM/J strain, instead of the A/J-7 strain. Based on the chromosomal constitution of Chr 7 in A/J-7A and A/J-7D mice, the causative gene for neonatal lethality in homosomic mice was suggested to be located within an approximately 1.

Two Loci Contribute to Age-Related Hearing Loss Resistance in the Japanese Wild-Derived Inbred MSM/Ms Mice.

An MSM/Ms strain was established using Japanese wild mice, which exhibit resistance to several phenotypes associated with aging, such as obesity, inflammation, and tumorigenesis, compared to common inbred mouse strains. MSM/Ms strain is resistant to age-related hearing loss, and their auditory abilities are sustained for long durations. The age-related hearing loss 3 () locus contributes to age-related hearing in MSM/Ms strain.

A novel model mouse for type 2 diabetes mellitus with early onset and persistent hyperglycemia.

Various mouse models of type 2 diabetes have been established, but few of these show early onset and persistent hyperglycemia. We have established a congenic mouse strain (NSY.B6-Tyr,A) in which a spontaneous mutation of the agouti yellow (A) gene, which causes obesity by hyperphagia, was introduced into the NSY strain, which shows increased glucose intolerance with age.

UVB-Induced Skin Autoinflammation Due to Mutation and Its Inhibition by Anti-IL-1β Antibody.

NLRP1 (NACHT and leucine-rich repeat-containing protein family, pyrin domain-containing protein 1) is an innate immune sensor that is involved in the formation of inflammasome complexes. NLRP1 hyperactivity has been reported to cause inherited autoinflammatory diseases including familial keratosis lichenoides chronica and NLRP1-associated autoinflammation with arthritis and dyskeratosis. We generated (the mouse homologue of human ) gain-of-function knock-in ( KI) mice with UVB irradiation-induced autoinflammatory skin lesions.

Structural basis for proteolytic processing of Aspergillus sojae α-glucosidase L with strong transglucosylation activity.

An α-glucosidase from Aspergillus sojae, AsojAgdL, exhibits strong transglucosylation activity to produce α-1,6-glucosidic linkages. The most remarkable structural feature of AsojAgdL is that residues 457-560 of AsojAgdL (designated the NC sequence) is not conserved in other glycoside hydrolase family 31 enzymes, and part of this NC sequence is proteolytically cleaved during its maturation. In this study, the enzyme was expressed in Pichia pastoris, and electrophoretic analysis indicated that the recombinant enzyme, rAsojAgdL, consisted of two polypeptide chains, as observed in the case of the enzyme produced in an Aspergillus strain.

A novel ENU-induced Cpox mutation causes microcytic hypochromic anemia in mice.

Mouse models of red blood cell abnormalities are important for understanding the underlying molecular mechanisms of human erythrocytic diseases. DBA.B6-Mha (Microcytic hypochromic anemia) congenic mice were generated from the cross between N-ethyl-N-nitrosourea (ENU)-mutagenized male C57BL/6J and female DBA/2J mice as part of the RIKEN large-scale ENU mutagenesis project.

E3 ubiquitin ligase RNF123-deficient mice exhibit reduced parasitemia and mortality in rodent malaria (Plasmodium yoelii 17XL) infection.

Increased levels of several human ubiquitin ligases, including ring finger protein 123 (RNF123), in red blood cells with Plasmodium falciparum infection, have been reported. RNF123 is an E3 ubiquitin ligase that is highly expressed in erythroid cells. However, the function of the RNF123 gene and the relationship between the RNF123 gene and malarial parasite has not been clarified in vivo.

Role of an Atypical Cadherin Gene, Cdh23 in Prepulse Inhibition, and Implication of CDH23 in Schizophrenia.

We previously identified quantitative trait loci (QTL) for prepulse inhibition (PPI), an endophenotype of schizophrenia, on mouse chromosome 10 and reported Fabp7 as a candidate gene from an analysis of F2 mice from inbred strains with high (C57BL/6N; B6) and low (C3H/HeN; C3H) PPI levels. Here, we reanalyzed the previously reported QTLs with increased marker density. The highest logarithm of odds score (26.

Ablation of Iah1, a candidate gene for diet-induced fatty liver, does not affect liver lipid accumulation in mice.

Nonalcoholic fatty liver disease (NAFLD) is a pathological condition caused by excess triglyceride deposition in the liver. The SMXA-5 severe fatty liver mouse model has been established from the SM/J and A/J strains. To explore the genetic factors involved in fatty liver development in SMXA-5 mice, we had previously performed quantitative trait locus (QTL) analysis, using (SM/J×SMXA-5)F2 intercross mice, and identified Fl1sa on chromosome 12 (centromere-53.

c.753A>G genome editing of a Cdh23 allele delays age-related hearing loss and degeneration of cochlear hair cells in C57BL/6J mice.

C57BL/6J mice have long been studied as a model of age-related hearing loss (ARHL). In C57BL/6J mice, ARHL begins in the high-frequency range at 3 months of age and spreads toward low frequencies by 10 months of age. We previously confirmed that c.

SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation.

The corneocyte lipid envelope, composed of covalently bound ceramides and fatty acids, is important to the integrity of the permeability barrier in the stratum corneum, and its absence is a prime structural defect in various skin diseases associated with defective skin barrier function. SDR9C7 encodes a short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7) recently found mutated in ichthyosis. In a patient with SDR9C7 mutation and a mouse Sdr9c7-KO model, we show loss of covalent binding of epidermal ceramides to protein, a structural fault in the barrier.

OHC-TRECK: A Novel System Using a Mouse Model for Investigation of the Molecular Mechanisms Associated with Outer Hair Cell Death in the Inner Ear.

Outer hair cells (OHCs) are responsible for the amplification of sound, and the death of these cells leads to hearing loss. Although the mechanisms for sound amplification and OHC death have been well investigated, the effects on the cochlea after OHC death are poorly understood. To study the consequences of OHC death, we established an OHC knockout system using a novel mouse model, Prestin-hDTR, which uses the prestin promoter to express the human diphtheria toxin (DT) receptor gene (hDTR).

Mouse NC/Jic strain provides novel insights into host genetic factors for malaria research.

Malaria is caused by Plasmodium parasites and is one of the most life-threatening infectious diseases in humans. Infection can result in severe complications such as cerebral malaria, acute lung injury/acute respiratory distress syndrome, and acute renal injury. These complications are mainly caused by P.

Congenic mapping and candidate gene analysis for streptozotocin-induced diabetes susceptibility locus on mouse chromosome 11.

Streptozotocin (STZ) has been widely used to induce diabetes in rodents. Strain-dependent variation in susceptibility to STZ has been reported; however, the gene(s) responsible for STZ susceptibility has not been identified. Here, we utilized the A/J-11 consomic strain and a set of chromosome 11 (Chr.