The Jeff Mouse Mutant Model for Chronic Otitis Media Manifests Gain-of-Function as Well as Loss-of-Function Effects
JavierSeptember 20, 20200 Comments
Chronic otitis media (OM) is the most common cause of hearing loss worldwide, but the underlying genetic and molecular pathology are poorly understood. Jeff mutant mouse is a mouse model for OM identified a single gene on the screen deaf as part of an ENU mutagenesis program at MRC Harwell. Jeff brings a missense mutation in the gene Fbxo11. Jeff heterozygous (Fbxo11 Jf / +) develop chronic OM at weaning and have reduced hearing.
Homozygous (Fbxo11 Jf / Jf) display perinatal lethal for the development of epithelial abnormality. In order to investigate the role FBXO11 and type of mutation responsible for the phenotype of mice Jeff, knock-out mouse models are created and compared to Jeff. Surprisingly, heterozygous knock-out (Fbxo11 tm2b / +) showed milder phenotype: they did not display any auditory deficits, and only some of them have thickened epithelial lining of the middle ear without fluid in the ear. In addition, the knock-out embryos homozygous (Fbxo11 tm2b / tm2b), as well as compound heterozygotes (Fbxo11 tm2b / Jf) show only mild abnormalities compared with homozygous Jeff (Fbxo11 Jf / Jf).
Interestingly, three days after inoculation intranasally of Fbxo11 tm2b / + mice with non-typeable Haemophilus influenzae (NTHI) proportion of them have been inflamed mucosa of the middle ear and accumulation of fluid in the ear indicates that Fbxo11 knock-out mice tend to NTHI induced inflammation of the middle ear. In conclusion, the finding that the mutant phenotype Jeff is much more severe than the knock-out show that a mutation in the manifest Jeff gain-of-function and loss-of-function effects on both embryonic and adult stages.
Congenital heart disease (CHD) affects nearly one percent of all live births. Despite advances in diagnostic and reparative surgery, causes and mechanisms of CHD is still mainly unknown. Extracellular matrix plays a major role in cell communication, function, and differentiation, and therefore may play a role in disease development and pathophysiology.
Cell adhesion and gap junction proteins, such as integrins and connexins, are also important for mobile communication and behavior, and can interact directly (integrins) or indirectly (connexins) with the extracellular matrix. In this work, we explore the gaps in the spatial pattern of expression and extracellular matrix, adhesion and gap junction protein between wild-type and Nkx2-5 + / RG mutant mice.
The Jeff Mouse Mutant Model for Chronic Otitis Media Manifests Gain-of-Function as Well as Loss-of-Function Effects
Nicotinamide riboside supplementation corrects deficits in oxytocin, socialization and anxiety of CD157 mutants in a mouse model of autism spectrum disorder
Oxytocin (OT) is an important molecule for social recognition and memory in social and emotional mediate behavior. In addition, PL act as a factor of anxiolytic and released during stress. Based on the activity of the enzyme that produces CD38 as calcium-mobilizing second messenger cyclic ADP-ribose (cADPR), CD157, CD38 sister protein, has been considered as candidate mediators for the production and release of OT and social engagement and anti-anxiety function.
However, the limited expression of CD157 in the adult rat brain undermines the trust participants molecule CD157 is authentic and / or followed up in social behavior OT-dependent. Here, we show that CD157 knockout mice had lower levels of circulating PL in the cerebrospinal fluid, which can be corrected by oral administration of nicotinamide riboside, vitamin precursor of nicotinamide adenine newfound dinucleotide (NAD).
cDNA - Human Adult Normal Tissue: Stomach: Pylorus
Description: Stomach tissue lysate was prepared by homogenization in modified RIPA buffer (150 mM sodium chloride, 50 mM Tris-HCl, pH 7.4, 1 mM ethylenediaminetetraacetic acid, 1 mM phenylmethylsulfonyl fluoride, 1% Triton X-100, 1% sodium deoxycholic acid, 0.1% sodium dodecylsulfate, 5 μg/ml of aprotinin, 5 μg/ml of leupeptin. Tissue and cell debris was removed by centrifugation. Protein concentration was determined with Bio-Rad protein assay. The product was boiled for 5 min in 1 x SDS sample buffer (50 mM Tris-HCl pH 6.8, 12.5% glycerol, 1% sodium dodecylsulfate, 0.01% bromophenol blue) containing 5% β-mercaptoethanol.
cDNA - Human Adult Normal Tissue: Heart: Ventricle (left)
Description: Stomach cancer tissue array with matched adjacent normal stomach tissue, including pathology grade, TNM and clinical stage, 40 cases/80 cores, replacing ST801a
cDNA - Human Adult Normal Tissue: Lung: Right Lower Lobe
Description: Stomach cancer with matched adjacent normal stomach tissue array, including pathology grade, TNM and clinical stage, 6cases/24cores, replacing ST244a
Description: Stomach cancer with adjacent normal tissue and normal tissue array, including pathology grade, TNM and clinical stage, 96 cases/192 cores, replacing ST2082
Description: Multiple stomach tumor with matched cancer adjacent or adjacent normal stomach tissue array, including pathology grade, TNM and clinical stage (reference AJCC 7th version), 40 cases/80 cores
Matched Pair - Total RNA - Human Primary Tumor and Normal Tissue: Stomach
Description: Stomach adenocarcinoma with matched adjacent normal tissue array, including TNM and pathology grade, 55 cases/100 cores(1.0mm), replacing ST1004
Matched Pair - Paraffin Tissue Sections - Human Primary Tumor and Normal (PP): Stomach
NAD is the substrate for CD157- and CD38 dependent cADPR production. nicotinamide riboside correcting social deficits and fear and anxiety-like behavior in male KO CD157. These results indicate that elevate NAD with nicotinamide riboside allow animals to cADPR- and OT-up the deficit to overcome this deficit and a more normal function.
