Skeletal Site-specific Changes in Bone Mass in a Genetic Mouse Model for Human 15q11-13 Duplication Seen in Autism

Kirsty Lewis, Kunal Sharan, Toru Takumi, Vijay Yadav

Research output: Contribution to journalArticle (Academic Journal)peer-review

18 Citations (Scopus)
357 Downloads (Pure)

Abstract

Children suffering from autism have been reported to have low bone mineral
density and increased risk for fracture, yet the cellular origin of the bone
phenotype remains unknown. Here we have utilized a mouse model of autism
that duplicates 6.3 Mb region of chromosome 7 (Dp/+) corresponding to a
region of chromosome 15q11-13, duplication of which is recurrent in humans to
characterize the bone phenotype. Paternally inherited Dp/+ (patDp/+) mice
showed expected increases in the gene expression in bone, normal postnatal
growth and body weight acquisition compared to the littermate controls. Four
weeks-old patDp/+ mice develop a low bone mass phenotype in the
appendicular but not the axial skeleton compared to the littermate controls. This
low bone mass in the mutant mice was secondary to a decrease in the number of
osteoblasts and bone formation rate while the osteoclasts remained relatively
unaffected. Further in vitro cell culture experiments and gene expression
analysis revealed a major defect in the proliferation, differentiation and
mineralization abilities of patDp/+ osteoblasts while osteoclast differentiation
remained unchanged compared to controls. This study therefore characterizes
the structural and cellular bone phenotype in a mouse model of autism that can
be further utilized to investigate therapeutic avenues to treat bone fractures in
children with autism.
Original languageEnglish
Article number9902
JournalScientific Reports
Volume7
Early online date29 Aug 2017
DOIs
Publication statusE-pub ahead of print - 29 Aug 2017

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