Morphological analyses of aberrant muscle innervation in DINE-deficient motor nerves

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860141
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Nagata Kenichi 国立研究開発法人理化学研究所, 脳科学総合研究センター, 基礎科学特別研究員 (50587798)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: DINE / ECEL1 / 先天性関節拘縮症 / 運動神経 / 軸索分岐 / CRISPR/Cas9 / ノックインマウス / 軸索伸展

Outline of Final Research Achievements

The membrane-bound metalloprotease endothelin-converting enzyme-like 1 (ECEL1) has been newly identified as a causal gene of a specific type of distal arthrogryposis (DA). In contrast to most causal genes of DA, ECEL1 is predominantly expressed in neuronal cells, suggesting a unique neurogenic pathogenesis in a subset of DA patients with ECEL1 mutation. The present study analyzed developmental motor innervation in the rodent homologue damage-induced neuronal endopeptidase (DINE)-deficient mouse limbs. Morphological analyses of motor innervation in over 10 different hindlimb muscles provided evidence that disruption of DINE gene leads to insufficient arborization of motor nerves after arriving at the skeletal muscle. Furthermore, we successfully generated several DINE knock-in mouse lines with a pathogenic DA mutation, and found motor innervation defects in the DINE mutant muscls. These results suggest that abnormal motor innervation could be a primary cause of DA with ECEL1 mutation.

Free Research Field

先天性関節拘縮症の発症原因をモデル動物を用いて探索している