2026-02-03 理化学研究所
ポリA配列(polyA)の違いによるマウスの脳での遺伝子発現特異性の変化
<関連情報>
- https://www.riken.jp/press/2026/20260203_1/index.html
- https://link.springer.com/article/10.1007/s00360-025-01648-7
ポリ(A)配列と遺伝要素がiCre発現とマウスの冬眠様状態の誘導に及ぼす影響 Influence of poly(A) sequences and genetic elements on iCre expression and induction of a hibernation-like state in mice
Hiroaki Ono,Takaya Abe,Kiyomi Ishikawa,Ayaka Wataki,Shoko Fujino,Makiya Matsumoto,Hiroshi Kiyonari & Genshiro A. Sunagawa
Journal of Comparative Physiology B Published:29 January 2026
DOI:https://doi.org/10.1007/s00360-025-01648-7
Abstract
Activation of hypothalamic QRFP-producing neurons (Q neurons) induces a hibernation-like state in mice, termed Q neurons–Induced Hypometabolism (QIH). To achieve reliable chemogenetic induction of QIH, precise expression of iCre in Q neurons is essential. Polyadenylation [poly(A)] cassettes, commonly included in knock-in constructs, not only stabilize transcripts but also influence transcription termination and expression specificity. Here we systematically compared three modifications of the Qrfp-iCre allele: (1) replacing the SV40 poly(A) with a bovine growth hormone (bGH) poly(A), (2) introducing bicistronic expression systems (T2A or IRES), and (3) deleting the poly(A) cassette to force reliance on the endogenous Qrfp poly(A) signal. The bGH poly(A) disrupted cell-type specificity and attenuated QIH, bicistronic constructs yielded largely specific but weak expression, and poly(A) deletion partially restored specificity and, in homozygotes, QIH depth, but shortened the duration. These findings demonstrate that poly(A) cassette choice is not a neutral design element but a critical determinant of both molecular and physiological outcomes, providing practical guidance for the design of neuronal knock-in models.
