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FAM20C is Essential for Maintaining Brain Homeostasis
Author(s) -
Zhang Hua,
Lu Yongbo,
Qin Chunlin
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.335.2
Subject(s) - knockout mouse , calcification , phenotype , homeostasis , biology , endocrinology , medicine , genetics , gene
OBJECTIVES FAM20C (Family with sequence similarity 20, member C) mutations cause Raine syndrome in humans, characterized by generalized osteosclerosis, distinctive craniofacial dysmorphism, along with extensive intracranial calcification. While much progress has been made in understanding the role of FAM20C in osteogenesis and odontogenesis, the function of FAM20C in brain is still unclear. The goal of this study was to determine whether FAM20C is required for normal brain homeostasis in vivo . METHODS 1) Reverse transcription polymerase chain reaction (RT‐PCR), Western‐blotting and in situ hybridization analyses were used to examine expression patterns of FAM20C in the mouse brain. 2) Global and conditional FAM20C‐knockout mice were generated by crossing FAM20C loxP mice with sox2‐cre (global) mice, Nestin‐cre (active in neuronal and glial cell precursors in brain) mice and 2.3 Col I‐Cre (active in osteoblasts/osteocytes in bone) mice, respectively. 3) A combination of histology, μ‐CT, and x‐ray methods were used to characterize the brain and bone phenotypes of the global and conditional FAM20C‐knockout mice. RESULTS 1) FAM20C was broadly expressed in the neuronal cells in the brain. 2) The global deletion (mediated by Sox‐2 cre) and brain‐specific (mediated by Nestin‐cre) deletion of Fam20C resulted in cerebral calcification in mice after postnatal 3 months and 6 months, respectively. Interestingly, although the bone‐specific (mediated by 2.3 Col I‐Cre) deletion, like the global deletion, of Fam20C caused similar hypophosphatemic rickets/osteomalacia in mice, it did not lead to intracranial calcification after postnatal 6 months. 3) X‐ray and histological analyses showed that the calcifications were bilaterally distributed within the brain. These calcifications were not associated with dystrophic changes. There were mild perifocal microgliosis as well as astrogliosis around calcospherites. CONCLUSIONS The local loss of FAM20C function in the brain may directly account for intracranial calcification. FAM20C may play an essential role in maintaining normal brain homeostasis and preventing ectopic brain calcification. Support or Funding Information NIH/NIDCR DE022549 to CQ This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .