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

التفاصيل البيبلوغرافية
العنوان: Cyclin M2 (CNNM2) knockout mice show mild hypomagnesaemia and developmental defects.
المؤلفون: Franken GAC; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands., Seker M; Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité - Universitätsmedizin Berlin, Berlin, Germany., Bos C; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands., Siemons LAH; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands., van der Eerden BCJ; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., Christ A; Department of Molecular Cardiovascular Research, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany., Hoenderop JGJ; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands., Bindels RJM; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands., Müller D; Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité - Universitätsmedizin Berlin, Berlin, Germany., Breiderhoff T; Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité - Universitätsmedizin Berlin, Berlin, Germany., de Baaij JHF; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands. jeroen.debaaij@radboudumc.nl.
المصدر: Scientific reports [Sci Rep] 2021 Apr 15; Vol. 11 (1), pp. 8217. Date of Electronic Publication: 2021 Apr 15.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Cation Transport Proteins/*genetics , Intellectual Disability/*genetics , Magnesium Deficiency/*genetics, Animals ; Animals, Newborn ; Embryo, Mammalian ; Female ; Intellectual Disability/blood ; Intellectual Disability/complications ; Intellectual Disability/pathology ; Magnesium/blood ; Magnesium Deficiency/blood ; Magnesium Deficiency/complications ; Magnesium Deficiency/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pregnancy ; Seizures/blood ; Seizures/complications ; Seizures/genetics
مستخلص: 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 Mg 2+ reabsorption. Here, we used a Cnnm2 knock out mouse model, generated by CRISPR/Cas9 technology, to assess the role of CNNM2 in Mg 2+ 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 Mg 2+ concentration compared to wildtype littermates. Subsequently, adult Cnnm2 +/- mice were fed with low, control, or high Mg 2+ diets for two weeks. Adult Cnnm2 +/- mice showed mild hypomagnesaemia compared to Cnnm2 +/+ mice and increased serum Ca 2+ levels, independent of dietary Mg 2+ intake. Faecal analysis displayed increased Mg 2+ and Ca 2+ 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 Mg 2+ homeostasis. Our data suggest a previously undescribed role of CNNM2 in the intestine, which may contribute to the Mg 2+ deficiency in mice and patients.
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المشرفين على المادة: 0 (Cation Transport Proteins)
0 (Cnnm2 protein, mouse)
I38ZP9992A (Magnesium)
تواريخ الأحداث: Date Created: 20210416 Date Completed: 20211203 Latest Revision: 20230131
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8050252
DOI: 10.1038/s41598-021-87548-6
PMID: 33859252
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-021-87548-6