The Shumiya cataract rat (SCR) is a hereditary cataractous strain. It is thought that the continuous occurrence of poorly differentiated epithelial cells at the bow area of the lens forms the pathophysiological basis for cataract formation in SCRs. In this study, we attempted to identify the genes associated with cataract formation in SCRs by positional cloning. Genetic linkage analysis revealed the presence of a major cataract locus on chromosome 20 as well as a locus on chromosome 15 that partially suppressed cataract onset. Hypomorphic mutations were identified in genes for lanosterol synthase (Lss) on chromosome 20 and farnesyl diphosphate farnesyl transferase 1 (Fdft1) on chromosome 15, both of which function in the cholesterol biosynthesis pathway. A null mutation for Lss was also identified. Cataract onset was associated with the specific combination of Lss and Fdft1 mutant alleles that decreased cholesterol levels in cataractous lenses to about 57% of normal. Thus, cholesterol insufficiency may underlie the deficient proliferation of lens epithelial cells in SCRs, which results in the loss of homeostatic epithelial cell control of the underlying fiber cells and eventually leads to cataractogenesis. These findings may have some relevance to other types of cataracts, inborn defects of cholesterol synthesis, and the effects of cholesterol-lowering medication.
Punicic acid, one of the conjugated linolenic acid (CLN) isomers, exerts a body-fat reducing effect. Although punicic acid is found in pomegranate and Tricosanthes kirilowii seeds, the amount of this fatty acid is very low in nature. The goal of this study was to produce a transgenic oil containing punicic acid. A cDNA encoding conjugase that converts linoleic acid to punicic acid was isolated from T. kirilowii, and the plant expression vector, pKN-TkFac, was generated. The pKN-TkFac was introduced into Brassica napus by Agrobacterium-mediated transformation. As a result, a genetically modified rapeseed oil (GMRO) containing punicic acid was obtained, although its proportion to the total fatty acids was very low (approximately 2.5%). The effects of feeding GMRO in ICR CD-1 male mice were then examined. Wild-type rapeseed (B. napus) oil (RSO) containing no CLN was used as a control oil. For reference oils, RSO-based blended oils were prepared by mixing with different levels of pomegranate oil (PO), either 2.5% (RSO + PO) or 5.0% (RSO + 2PO) punicic acid. Mice were fed purified diets containing 10% of either RSO, RSO + PO, RSO + 2PO, or GMRO for 4 weeks, and dietary PO dose-dependently reduced perirenal adipose tissue weight with a significant difference between the RSO group and the RSO + 2PO group. GMRO, as compared to RSO, lowered the adipose tissue weight to the levels observed with RSO + 2PO. The liver triglyceride level of the RSO + 2PO and GMRO groups but not that of the RSO + PO group was lower than that of the RSO group. The RSO + 2PO and GMRO groups, but not the RSO + PO group, had increased carnitine-palmitoyltransferase activity in the liver and brown adipose tissue. These results showed that dietary GMRO, even at a dietary punicic acid level as low as 0.25 wt % of diet, reduced body fat mass and altered liver lipid metabolism in mice and was more effective than an equal amount of punicic acid from PO.
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