Vps4bヘテロ接合マウスは、ヒト象牙質形成不全Iを再現する歯の欠損を発症しない

Vps4b heterozygous mice do not develop tooth defects that replicate human dentin dysplasia I.

• Aiqin Hu
• Ting Lu
• Danna Chen
• Jin Huang
• Weiwei Feng
• Yanjun Li
• Dan Guo
• Xiangmin Xu
• Dong Chen
• Fu Xiong

抄録

背景:

液胞蛋白質選別関連蛋白質4B（VPS4B）は、ATP酵素AAA蛋白質ファミリーの一種であり、主に蛋白質分解や細胞膜融合に関与している。近年、ヒト象牙質形成不全I型（DD-I）において、この遺伝子の優性変異が同定された。ここでは、Vps4bノックアウト（Vps4b KO）マウスの作製を報告するが、ホモ接合体のVps4b KO変異は胚発生初期に胚性致死性を示したため、ヘテロ接合体変異マウスの作製結果を報告する。

BACKGROUND: Vacuolar protein sorting-associated protein 4B (VPS4B) is a member of the ATP enzyme AAA protein family, and is mainly involved in protein degradation and cell membrane fusion. Recently, a dominant mutation in this gene was identified in human dentin dysplasia type I (DD-I). Herein, we report the generation of Vps4b knockout (Vps4b KO) mice; however, the homozygous Vps4b KO mutation was embryonic lethal at the early stages of embryo development, and we therefore report the results of heterozygous mutant mice.

結果:

RESULTS: Mice heterozygous for Vps4b did not develop tooth defects replicating human DD-I. Immunohistochemistry showed that gene KO was successful, as there was decreased expression of Vps4b in heterozygous mice; hematoxylin and eosin (H&E) staining also showed that the width of the pre-dentin zone was increased in heterozygous mice, although the arrangement of the odontoblasts was not significantly different from wild-type (WT) mice. However, H&E staining showed no obvious abnormalities in the bones of heterozygous mice. Moreover, stereomicroscopic and X-ray radiography results indicated no abnormal manifestations in teeth or bones. Furthermore, statistical analysis of the volume and density of dentin and enamel, as well as skeletal analysis, including the volume and separation of trabecular bone analyzed by micro-CT, all showed no differences between Vps4b heterozygotes and WT mice. In addition, there also were no significant differences in bone or cartilage mineralization as evaluated by Alcian blue-Alizarin red staining.

結論:

ヘテロ接合体の Vps4b KO マウスでは、ヒトの DD-I を再現するような歯の欠損は見られず、これは両種間の歯の発育の違いによるものと考えられる。したがって、マウスがヒトの歯の病気のモデルとして適切な動物であるかどうかを判断するためには、さらなる研究が必要である。

CONCLUSIONS: The heterozygous Vps4b KO mice do not develop tooth defects that replicate human DD-I and this is likely to be due to differences in tooth development between the two species. Consequently, further studies are needed to determine whether mice are an appropriate animal model for human tooth diseases.