• Makoto Handa, Satoru Demura, Noriaki Yokogawa, Eiichi Hinoi, Manami Hiraiwa, Satoshi Kato, Kazuya Shinmura, Ryohei Annen, Motoya Kobayashi, Yohei Yamada, Satoshi Nagatani, Yuki Kurokawa, and Hiroyuki Tsuchiya.
• Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
• Spine. 2024 Feb 15; 49 (4): 285293285-293.

Study DesignA mouse study of the Slc7a5 gene using conditional knockout to assess the effects of its inactivation on spinal deformity.ObjectivesThis study aimed to investigate whether the mice with scoliosis [induced by chondrocyte-specific inactivation of L-type amino acid transporter 1 (LAT1)] show a developmental process similar to that of pediatric scoliosis and to examine the relationship between reduced bone mineral density (BMD) and scoliosis. Furthermore, we aimed to obtain insights into elucidating the etiology and pathophysiology of scoliosis.Summary Of Background DataThe etiology and pathogenesis of scoliosis are not fully understood despite substantial investigative efforts. LAT1 is an amino acid transporter that mediates the cellular uptake of large neutral amino acids. A recent study revealed that chondrocyte-specific inactivation of LAT1 in mice results in scoliosis (Col2a1-Cre;Slc7a5fl/fl mice: "Sko mice").Materials And MethodsBody length, body weight, Cobb angle, vertebral body rotation angle, and BMD at 1, 2, 4, 6, and 8 weeks of age were examined and statistically compared with those of normal control mice. Pathologic and morphologic evaluation was performed on specimens from 10-week-old euthanized mice.ResultsThe Sko mice developed thoracic scoliosis in infancy without congenital malformations. This spinal deformity progressed rapidly during growth, with diverse curve patterns and hypoplastic vertebral bodies. Pathologic examination revealed thickening of the growth plates and decreased osteoblasts, suggesting that impaired endochondral ossification was the cause of the scoliosis. Sko mice were also observed to have decreased BMD and degraded bone microstructure. Reduced BMD and bone quality may not be the causes of the onset and progression of scoliosis in the Sko mice.ConclusionsIn Sko mice, the characteristics of scoliosis and vertebral pathology showed many similarities with syndromic scoliosis in humans. Endochondral ossification defects may impair growth, leading to scoliosis and decreased BMD.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

15 keywords...

hide…