Details

Autor(en) / Beteiligte

• Franken, Gijs A. C.
• Seker, Murat
• Bos, Caro
• Siemons, Laura A. H.
• van der Eerden, Bram C. J.
• Christ, Annabel
• Hoenderop, Joost G. J.
• Bindels, René J. M.
• Müller, Dominik
• Breiderhoff, Tilman
• de Baaij, Jeroen H. F.

Titel

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

Ist Teil von

• Scientific reports, 2021-04, Vol.11 (1), p.8217-8217, Article 8217

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.