RESUMEN
C57BL/6J (BL6J) and C57BL/6N (BL6N) inbred substrains are most widely used to understand the pathological roles of target molecules in a variety of diseases, including non-alcoholic steatohepatitis (NASH), based on transgenic mouse technologies. There are notable differences in the metabolic phenotypes, including glucose tolerance, between the BL6J and BL6N substrains, but the phenotypic differences in NASH are still unknown. We performed a comparative analysis of the two mouse substrains to identify the pathological phenotypic differences in NASH models. In the CCl4-induced NASH model, the BL6J mice exhibited a more severe degree of oxidative stress and fibrosis in the liver than the BL6N mice. In contrast, in the high-fat diet-induced NASH model, more accumulation of hepatic triglycerides but less weight gain and liver injury were noted in the BL6J mice than in the BL6N mice. Our findings strongly suggest caution be exercised with the use of unmatched mixed genetic background C57BL6 mice for studies related to NASH, especially when generating conditional knockout C57BL6 mice.
Asunto(s)
Hígado/metabolismo , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/patología , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Femenino , Fibrosis , Masculino , Ratones , Ratones Endogámicos C57BL/genética , Ratones Endogámicos , Ratones Noqueados , Ratones Transgénicos , Enfermedad del Hígado Graso no Alcohólico/genética , Estrés Oxidativo/fisiología , Fenotipo , Aumento de PesoRESUMEN
A highly efficient direct asymmetric aldol reaction of a glycinate Schiff base with aldehydes has been achieved under mild organic/aqueous biphasic conditions with excellent stereochemical control, using chiral quaternary ammonium salt 1b as a phase-transfer catalyst. The initially developed reaction conditions, using 2 equiv of aqueous base (1% NaOH (aq)), exhibited inexplicably limited general applicability in terms of aldehyde acceptors. The mechanistic investigation revealed the intervention of an unfavorable yet inevitable retro aldol process involving the chiral catalyst. On the basis of this information, a reliable procedure has been established by use of a catalytic amount of 1% NaOH (aq) and ammonium chloride, which tolerates a wide range of aldehydes to afford the corresponding anti-beta-hydroxy-alpha-amino esters almost exclusively in an essentially optically pure form.