Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome
Abstract Background Inactivation or mutations of FAM20C causes human Raine Syndrome, which manifests as lethal osteosclerosis bone dysplasia or non-lethal hypophosphatemia rickets. However, it is only hypophosphatemia rickets that was reported in the mice with Fam20c deletion or mutations. To furthe...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12860-024-00526-4 |
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| author | Mengnan Chen Dongmei Sun Siu-Pok Yee Zhaoyang Yuan Li Lin Bing Cui Yi Wang Chao Liu Peihong Liu |
| author_facet | Mengnan Chen Dongmei Sun Siu-Pok Yee Zhaoyang Yuan Li Lin Bing Cui Yi Wang Chao Liu Peihong Liu |
| author_sort | Mengnan Chen |
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| description | Abstract Background Inactivation or mutations of FAM20C causes human Raine Syndrome, which manifests as lethal osteosclerosis bone dysplasia or non-lethal hypophosphatemia rickets. However, it is only hypophosphatemia rickets that was reported in the mice with Fam20c deletion or mutations. To further investigate the local and global impacts of Fam20c mutation, we constructed a knock-in allele carrying Fam20c mutation (D446N) found in the non-lethal Raine Syndrome. The Fam20c D446N allele replaced the WT Fam20c by 3.6Kb Col1a1-Cre to get the conditional knock-in mice, and by Hprt-cre to get conventional knock-in mice, respectively. Results The radiology, serum biochemistry and immunohistochemistry indicated that all conditional and most conventional Fam20c D446N knock-in mice displayed hypophosphatemic rickets with the increased Fgf23 and deceased Dmp1 expression, which survived to adulthood. However, a few conventional Fam20c D446N knock-in mice died before weaning with the osteosclerotic X-ray radiography, though micro-CT assay displayed a reduced mineral density and increased porosity in the osteosclerotic tibia. Our results suggested that hypophosphatemia rickets was the predominant phenotype in both conditional and conventional Fam20c deficient mice, while the lethal osteosclerotic phenotype occasionally took place in the conventional Fam20c mutant mice. Conclusion This finding also implicated that the osteosclerotic features resulting from Fam20c deficiency could be a semblance on the basis of rickets, which is most likely triggered by the alterations in the systems other than skeleton. |
| format | Article |
| id | doaj-art-f526bef1495f433e8eaefd69381a9116 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Molecular and Cell Biology |
| spelling | doaj-art-f526bef1495f433e8eaefd69381a91162025-01-05T12:49:48ZengBMCBMC Molecular and Cell Biology2661-88502025-01-0126111010.1186/s12860-024-00526-4Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine SyndromeMengnan Chen0Dongmei Sun1Siu-Pok Yee2Zhaoyang Yuan3Li Lin4Bing Cui5Yi Wang6Chao Liu7Peihong Liu8Department of Stomatology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Stomatology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cell Biology, Health Science Center, University of ConnecticutDepartment of Stomatology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Stomatology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Stomatology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Prosthodontics, School of Stomatology, Dalian Medical UniversityDepartment of Oral Pathology, School of Stomatology, Dalian Medical UniversityDepartment of Stomatology, The First Affiliated Hospital of Harbin Medical UniversityAbstract Background Inactivation or mutations of FAM20C causes human Raine Syndrome, which manifests as lethal osteosclerosis bone dysplasia or non-lethal hypophosphatemia rickets. However, it is only hypophosphatemia rickets that was reported in the mice with Fam20c deletion or mutations. To further investigate the local and global impacts of Fam20c mutation, we constructed a knock-in allele carrying Fam20c mutation (D446N) found in the non-lethal Raine Syndrome. The Fam20c D446N allele replaced the WT Fam20c by 3.6Kb Col1a1-Cre to get the conditional knock-in mice, and by Hprt-cre to get conventional knock-in mice, respectively. Results The radiology, serum biochemistry and immunohistochemistry indicated that all conditional and most conventional Fam20c D446N knock-in mice displayed hypophosphatemic rickets with the increased Fgf23 and deceased Dmp1 expression, which survived to adulthood. However, a few conventional Fam20c D446N knock-in mice died before weaning with the osteosclerotic X-ray radiography, though micro-CT assay displayed a reduced mineral density and increased porosity in the osteosclerotic tibia. Our results suggested that hypophosphatemia rickets was the predominant phenotype in both conditional and conventional Fam20c deficient mice, while the lethal osteosclerotic phenotype occasionally took place in the conventional Fam20c mutant mice. Conclusion This finding also implicated that the osteosclerotic features resulting from Fam20c deficiency could be a semblance on the basis of rickets, which is most likely triggered by the alterations in the systems other than skeleton.https://doi.org/10.1186/s12860-024-00526-4FAM20CRaine syndromeOsteosclerosisHypophosphataemic ricketsBiomineralization |
| spellingShingle | Mengnan Chen Dongmei Sun Siu-Pok Yee Zhaoyang Yuan Li Lin Bing Cui Yi Wang Chao Liu Peihong Liu Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome BMC Molecular and Cell Biology FAM20C Raine syndrome Osteosclerosis Hypophosphataemic rickets Biomineralization |
| title | Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome |
| title_full | Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome |
| title_fullStr | Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome |
| title_full_unstemmed | Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome |
| title_short | Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome |
| title_sort | mutant fam20c knock in mice recapitulate both lethal and non lethal human raine syndrome |
| topic | FAM20C Raine syndrome Osteosclerosis Hypophosphataemic rickets Biomineralization |
| url | https://doi.org/10.1186/s12860-024-00526-4 |
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