Improvements in metabolic parameters and histopathological scores show that correction of the Dmo1 genetic pathway in the diabetic and mildly obese OLETF rat strain produces wide-ranging therapeutic effects. Thus, this pathway might represent a new drug target also applicable to humans.
Epithelial papillary hyperplasia of choledocho-pancreatic duct, associated with cellular atypism, was observed in Otsuka Long Evans Tokushima Fatty (OLETF) rats, a strain originally established as an animal model for non-insulin-dependent diabetes mellitus (NIDDM). To investigate the potential feasibility of OLETF rats as an animal model for pancreatic ductal carcinoma, we examined the pathological characteristics of ductal lesions in OLETF rats aged from 5 to 50 weeks. Hyperplastic lesions in OLETF rats became apparent after 10 weeks of age and increased in severity and frequency of atypical changes in hyperplastic epithelium appearing after 20 weeks. We compared ductal lesions from OLETF rats with those from age-matched Long Evans Tokushima Otsuka (LETO) rats, which share a similar genetic background with OLETF rats but do not develop NIDDM. While LETO rats also display a tendency toward ductal hyperplasia, lesions from OLETF rats were more numerous and larger in size than those from age-matched LETO rats. In addition, lesions from OLETF rats contained a significantly higher number of proliferating cell nuclear antigen-positive cells than those from LETO rats. Finally, lesions in OLETF rats were accompanied by inflammation, and the observed morphological alteration of lesions correlated well with the grade of inflammation.
Following gene duplication events, the expression patterns of the resulting gene copies can often diverge both spatially and temporally. Here we report on gene duplicates that are expressed in distinct but overlapping patterns, and which exhibit temporally divergent expression. Butterflies have sophisticated color vision and spectrally complex eyes, typically with three types of heterogeneous ommatidia. The eyes of the butterfly Papilio xuthus express two green- and one red-absorbing visual pigment, which came about via gene duplication events, in addition to one ultraviolet (UV)- and one blue-absorbing visual pigment. We localized mRNAs encoding opsins of these visual pigments in developing eye disks throughout the pupal stage. The mRNAs of the UV and blue opsin are expressed early in pupal development (pd), specifying the type of the ommatidium in which they appear. Red sensitive photoreceptors first express a green opsin mRNA, which is replaced later by the red opsin mRNA. Broadband photoreceptors (that coexpress the green and red opsins) first express the green opsin mRNA, later change to red opsin mRNA and finally re-express the green opsin mRNA in addition to the red mRNA. Such a unique temporal and spatial expression pattern of opsin mRNAs may reflect the evolution of visual pigments and provide clues toward understanding how the spectrally complex eyes of butterflies evolved.
An Otsuka Long-Evans Tokushima Fatty (OLETF) strain of rat spontaneously developed hyperglycemia, hyperinsulinemia, insulin resistance and mild obesity, which had been studied as animal model for type II diabetes mellitus (T2DM). Recently, we observed that this strain coincidentally developed atypical hyperplasia of the choledocho-pancreatic ductal epithelium with a complete incidence. In an effort to locate genes responsible for this hyperplasia, we prepared 288 backcross progeny from a mating between OLETF rats and BN rats (which do not develop hyperplasia), and performed a genome-wide scan using 207 polymorphic genetic markers. We observed a prominent association of hyperplasia with a region involving a marker locus D14Mit4 (P = 0.00020, Fisher's exact test) and Cckar (the cholecystokinin-A receptor gene; P = 0.00025, Fisher's exact test) which is known to be disrupted in an OLETF strain. Our findings indicated that epithelial hyperplasia of the choledocho-pancreatic duct is associated with a region on rat chromosome 14 around the Cckar gene in an additive fashion with another two susceptible loci, each on chromosome 9 and 7. This implied the possibility that Cckar deficiency could result in a predisposition towards pancreatic duct hyperplasia.
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