Dataset Information

Mouse Samd9l is not a functional paralogue of the human SAMD9, the gene mutated in normophosphataemic familial tumoral calcinosis.

ABSTRACT: Normophosphataemic familial tumoral calcinosis, charac-terized by ectopic mineralization of skin, is caused by mutations in the SAMD9 gene located in human chromosome 7q21, next to a paralogous gene, SAMD9-like (SAMD9L). The mouse does not have a SAMD9 orthologue, Samd9, because it has been deleted during evolution owing to genomic rearrangements. It has been suggested that the mouse Samd9l gene serves as a functional paralogue of human SAMD9. In this study, we examined Samd9l knockout mice with respect to ectopic mineralization. We also crossed these mice with Abcc6(tm1JfK) mice, a model system to study pseudoxanthoma elasticum, to see whether the absence of the Samd9l gene modifies the mineralization process. Necropsy analysis of Samd9l(tm1Homy) mice revealed no evidence of ectopic mineralization, and deletion of the Samd9l gene in mice failed to modify the mineralization process on the Abcc6(tm1JfK) background. Collectively, the results suggest that mouse Samd9l is not a functional paralogue of human SAMD9.

SUBMITTER: Li Q

PROVIDER: S-EPMC3381902 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Mouse Samd9l is not a functional paralogue of the human SAMD9, the gene mutated in normophosphataemic familial tumoral calcinosis.

Li Qiaoli Q Guo Haitao H Matsui Hirotaka H Honda Hiroaki H Inaba Toshiya T Sundberg John P JP Sprecher Eli E Uitto Jouni J

Experimental dermatology 20120701 7

Normophosphataemic familial tumoral calcinosis, charac-terized by ectopic mineralization of skin, is caused by mutations in the SAMD9 gene located in human chromosome 7q21, next to a paralogous gene, SAMD9-like (SAMD9L). The mouse does not have a SAMD9 orthologue, Samd9, because it has been deleted during evolution owing to genomic rearrangements. It has been suggested that the mouse Samd9l gene serves as a functional paralogue of human SAMD9. In this study, we examined Samd9l knockout mice with ...[more]

PMID: 22716256

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Project description:BACKGROUND:The physiological functions of the human Sterile Alpha Motif Domain-containing 9 (SAMD9) gene and its chromosomally adjacent paralogue, SAMD9-like (SAMD9L), currently remain unknown. However, the direct links between the deleterious mutations or deletions in these two genes and several human disorders, such as inherited inflammatory calcified tumors and acute myeloid leukemia, suggest their biological importance. SAMD9 and SAMD9L have also recently been shown to play key roles in the innate immune responses to stimuli such as viral infection. We were particularly interested in understanding the mammalian evolutionary history of these two genes. The phylogeny of SAMD9 and SAMD9L genes was reconstructed using the Maximum Likelihood method. Furthermore, six different methods were applied to detect SAMD9 and SAMD9L codons under selective pressure: the site-specific model M8 implemented in the codeml program in PAML software and five methods available on the Datamonkey web server, including the Single Likelihood Ancestor Counting method, the Fixed Effect Likelihood method, the Random Effect Likelihood method, the Mixed Effects Model of Evolution method and the Fast Unbiased Bayesian AppRoximation method. Additionally, the house mouse (Mus musculus) genome has lost the SAMD9 gene, while keeping SAMD9L intact, prompting us to investigate whether this loss is a unique event during evolution. RESULTS:Our evolutionary analyses suggest that SAMD9 and SAMD9L arose through an ancestral gene duplication event after the divergence of Marsupialia from Placentalia. Additionally, selection analyses demonstrated that both genes have been subjected to positive evolutionary selection. The absence of either SAMD9 or SAMD9L genes from some mammalian species supports a partial functional redundancy between the two genes. CONCLUSIONS:To the best of our knowledge, this work is the first study on the evolutionary history of mammalian SAMD9 and SAMD9L genes. We conclude that evolutionary selective pressure has acted on both of these two genes since their divergence, suggesting their importance in multiple cellular processes, such as the immune responses to viral pathogens.

Dataset Information

Mouse Samd9l is not a functional paralogue of the human SAMD9, the gene mutated in normophosphataemic familial tumoral calcinosis.

Publications

Mouse Samd9l is not a functional paralogue of the human SAMD9, the gene mutated in normophosphataemic familial tumoral calcinosis.

Similar Datasets

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