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Conditional Deletion of Cytochrome P450 Reductase in Mouse Bone Results in Antley‐Bixler Syndrome‐Like Craniofacial and Bone Mass Defects
Author(s) -
Panda Satya Prakash,
Guntur Anyonya R.,
Kar Rekha,
Tang Kejian,
Masters Betties Sue
Publication year - 2012
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.26.1_supplement.784.8
Subject(s) - calvaria , conditional gene knockout , craniofacial , biology , phenotype , endocrinology , medicine , genetics , in vitro , gene
NADPH‐cytochrome P450 oxido‐reductase (CYPOR) is the obligate electron donor for cytochromes P450, dehydrocholesterol reductase, heme oxygenase, and squalene monooxygenase. Genetic screening of patients had revealed the presence of mutations in CYPOR leading to severe developmental defects including sexual ambiguities and various bone defects such as craniosynostosis and mid‐face hypoplasia, originally described by Antley and Bixler (1975). To probe the possible roles played by CYPOR during bone development, we have generated a conditional knockout (CKO) mice using cross‐bred Cpr lox/lox and Dermo1 Cre mice. Since the Dermo1 Cre recombinase is active from 9.5 dpc, CYPOR is deleted in both chondrocytes and osteoblasts in the CKO mice. Here we report the first mouse model showing craniofacial abnormalities upon deletion of CYPOR in bone. Differential staining of CKO mice skulls show premature fusion of spheno‐occipital synchondroses and anterior intraoccipital synchondroses. Teeth malocclusion was noticed in the adult CKO mice. Micro CT analysis of the tibia revealed that deletion of CYPOR leads to a reduction in the bone mineral density compared in age‐ and sex‐matched littermate controls, with cortical bone thickness remaining unaffected. These results recapitulate the human CYPOR deficiency phenotype and offer an approach to study the phenotypic sequelae of CYPOR mutations. Supported by GM081568 to BSM