Cyclin M2 (CNNM2) knockout mice show mild hypomagnesaemia and developmental defects.

Patients with mutations in Cyclin M2 (CNNM2) suffer from hypomagnesaemia, seizures, and intellectual disability. Although the molecular function of CNNM2 is under debate, the protein is considered essential for renal Mg2+ reabsorption. Here, we used a Cnnm2 knock out mouse model, generated by CRISPR/Cas9 technology, to assess the role of CNNM2 in Mg2+ homeostasis. Breeding Cnnm2+/- mice resulted in a Mendelian distribution at embryonic day 18. Nevertheless, only four Cnnm2-/- pups were born alive. The Cnnm2-/- pups had a significantly lower serum Mg2+ concentration compared to wildtype littermates. Subsequently, adult Cnnm2+/- mice were fed with low, control, or high Mg2+ diets for two weeks. Adult Cnnm2+/- mice showed mild hypomagnesaemia compared to Cnnm2+/+ mice and increased serum Ca2+ levels, independent of dietary Mg2+ intake. Faecal analysis displayed increased Mg2+ and Ca2+ excretion in the Cnnm2+/- mice. Transcriptional profiling of Trpm6, Trpm7, and Slc41a1 in kidneys and colon did not reveal effects based on genotype. Microcomputed tomography analysis of the femurs demonstrated equal bone morphology and density. In conclusion, CNNM2 is vital for embryonic development and Mg2+ homeostasis. Our data suggest a previously undescribed role of CNNM2 in the intestine, which may contribute to the Mg2+ deficiency in mice and patients.

Mouse Models of Human Claudin-Associated Disorders: Benefits and Limitations.

In higher organisms, epithelia separate compartments in order to guarantee their proper function. Such structures are able to seal but also to allow substances to pass. Within the paracellular pathway, a supramolecular structure, the tight junction transport is largely controlled by the temporospatial regulation of its major protein family called claudins. Besides the fact that the expression of claudins has been identified in different forms of human diseases like cancer, clearly defined mutations in the corresponding claudin genes have been shown to cause distinct human disorders. Such disorders comprise the skin and its adjacent structures, liver, kidney, the inner ear, and the eye. From the phenotype analysis, it has also become clear that different claudins can cause a complex phenotype when expressed in different organs. To gain deeper insights into the physiology and pathophysiology of claudin-associated disorders, several mouse models have been generated. In order to model human disorders in detail, they have been designed either as full knockouts, knock-downs or knock-ins by a variety of techniques. Here, we review human disorders caused by CLDN mutations and their corresponding mouse models that have been generated thus far and assess their usefulness as a model for the corresponding human disorder.

Determination and comparison of chemical characteristics of Arbutus unedo L. and Arbutus andrachnae L. (family Ericaceae) fruits.

The fruits and leaves of Arbutus species are well known in folk medicine as antiseptics, diuretics, and laxatives in many parts of Turkey. Some chemical properties including pH, soluble solid content, titratable acidity, protein, moisture, ash, ascorbic acid, fructose, glucose, sucrose, total phenols, total antioxidant activity, and minerals were determined in fully matured Arbutus unedo L. and Arbutus andrachnae L. fruits collected from different sites of Canakkale, Turkey in 2006 and 2007. Total soluble solids, titratable acidity, protein, moisture, and ash content of A. unedo and A. andrachnae berries were on average 16.0% and 14.0%, 0.4% and 0.6%, 2.38% and 3.77%, 47.21% and 38.21%, and 2.82% and 4.35%, respectively. The mean values of ascorbic acid were 270.50 mg/100 g for A. unedo and 140.30 mg/100 g for A. andrachnae, which suggested that Arbutus berries contain high amounts of vitamin C. In the strawberry tree fruits, fructose and glucose were determined to be the major sugars. The analysis showed that fructose and glucose occurred in concentrations of 24.09% and 19.09%, respectively. However, ripe A. andrachnae fruits contained small amounts of fructose (4.12%), glucose (2.73%), and sucrose (0.16%) detectable by high-performance liquid chromatography analysis. The general order of abundance of the minerals was K > Ca > P > Mg > Na in whole fruit of the strawberry tree. The chemical composition of Arbutus fruits indicates that the fruits are good sources of minerals and ascorbic acid and that they are high in phenolics and antioxidant capacity and low in soluble sugars, especially A. andrachnae. The data should be useful for research purposes and for compiling local food composition tables. In view of its chemical composition, the use of Arbutus fruits in some food products may be suggested.

Screening and comparing tocopherols in the rapeseed (Brassica napus L.) and olive (Olea europaea L.) varieties using high-performance liquid chromatography.

Rapeseed and virgin olive oils are a good source of tocopherols. Tocopherols are the most important compounds having antioxidant activity in both crops. Little is known about the tocopherol contents of rapeseed and olive oil grown in Turkey. The aims of this research were to investigate some new rapeseed varieties and olive genotypes grown in northwest Turkey and to compare the tocopherol fractions and contents of both crops. For rapeseed, the data were collected in two growing seasons (2004-2005, 2005-2006) from a field experiment with 19 new rapeseed varieties. For olives, virgin olive oils produced from 21 different varieties were examined in the 2004-2005 and 2005-2006 growing seasons. The separation and identification of tocopherols and the analysis of their contents were successfully achieved using the high-performance liquid chromatographic method. According to the obtained results, gamma-tocopherol (44.200-118.900 mg/kg) was the major fraction of total tocopherol, followed by alpha-tocopherol (19.300-68.500 mg/kg) and delta-tocopherol (0.00-2.600 mg/kg) for rapeseeds. Regarding olive varieties, the alpha-tocopherol content changed between 52.000 and 194.750 mg/kg, followed by gamma-tocopherol ranging from 0.00 to 39.750 mg/kg. The total tocopherol content ranged between 83.900 and 173.800 mg/kg for rapeseed and between 52.100 and 213.075 mg/kg for olives. This study revealed that an important variability exists for tocopherol content and composition in rapeseed and olive varieties.