Strain Data Sheet

RBRC06344

Strain Information

Image
BRC No.RBRC06344
TypeTargeted MutationCartagena
SpeciesMus musculus
Strain nameC57BL/6-App<tm3(NL-G-F)Tcs>
Former Common nameAPP<NL-G-F>, B6-App/NL-G-F KI
H-2 Haplotype
ES Cell lineiTL IC1 [C57BL/6NTac]
Background strain
Appearance
Strain development理化学研究所脳科学総合研究センター・齋藤貴志先生、西道隆臣先生(2009)。C57BL/6由来ES細胞を用いて作出。NeoカセットはEIIa-creマウス(B6.FVB-Tg(EIIa-cre)C5379Lmgd/J)との交配により除去。C57BL/6背景。
Strain descriptionマウスApp遺伝子のアミロイドβ領域に遺伝子変異を挿入したノックインマウス。マウスアミロイドβ配列のヒト化に加え、家族性アルツハイマー病変異のSwedish変異単独 (App<NL>ノックイン、RBRC06342) 、Iberian変異との2重変異 (App<NL-F>ノックイン、RBRC06343) 、さらにArctic変異を加えた3重変異 (App<NL-G-F>ノックイン、RBRC06344) を導入。ホモマウスは生存性、繁殖性あり。毒性アミロイドβ種 (Aβ42) の産生比率を高め、若齢からアミロイド班を形成する (App<NL>ノックインマウスは陰性コントロールとして利用) 。App<NL-F>ホモマウスは6ヶ月齢から、App<NL-G-F>ホモマウスは2ヶ月齢から脳内においてアミロイド班が形成される。アミロイド班の形成に伴い、神経炎症およびシナプスの脱落が認められる。さらに、App<NL-F>ホモマウスは18ヶ月齢から、App<NL-G-F>ノックインマウスは6ヶ月齢からY迷路における行動異常が認められる。アルツハイマー病研究において重要なモデルマウス。
Colony maintenanceHomozygote x Homozygote [or Crossing to C57BL/6J(Crl)]
References
Recent Advances in the Modeling of Alzheimer's Disease.
Hiroki Sasaguri, Shoko Hashimoto, Naoto Watamura, Kaori Sato, Risa Takamura, Kenichi Nagata, Satoshi Tsubuki, Toshio Ohshima, Atsushi Yoshiki, Kenya Sato, Wakako Kumita, Erika Sasaki, Shinobu Kitazume, Per Nilsson, Bengt Winblad, Takashi Saito, Nobuhisa Iwata, Takaomi C Saido
Front. Neurosci., 16:807473 (2022). 35431779

Single App knock-in mouse models of Alzheimer's disease.
Saito T, Matsuba Y, Mihira N, Takano J, Nilsson P, Itohara S, Iwata N, Saido T C
Nat. Neurosci., 17(5):661-663 (2014). 24728269

Health Report

Examination Date / Room / Rack2024/04/08Room:3-ARack:A
2024/01/09Room:3-ARack:D
2023/10/10Room:3-ARack:A and D
2023/07/10Room:3-ARack:D
2023/04/10Room:3-ARack:D
2023/02/13Room:3-ARack:D
2023/01/10Room:3-ARack:D
2022/12/05Room:3-ARack:D
2022/10/11Room:3-ARack:D

Gene

Gene SymbolGene NameChr.Allele SymbolAllele NameCommon NamesPromoterDiseases Related to This Gene
Appamyloid beta precursor protein16Apptargeted mutation 3, Takaomi C. Saido
  • Alzheimer disease type 1(MedGEN)

  • Alzheimer disease(DisGeNET)

  • cerebral amyloid angiopathy, APP-related(MedGEN)
  • Frtyeast FRT (flippase recombination target) site16Frt
  • Alzheimer disease type 1(MedGEN)

  • Alzheimer disease(DisGeNET)

  • cerebral amyloid angiopathy, APP-related(MedGEN)
  • loxPphage P1 loxP16loxP
  • Alzheimer disease type 1(MedGEN)

  • Alzheimer disease(DisGeNET)

  • cerebral amyloid angiopathy, APP-related(MedGEN)
  • Phenotype

    Annotation by Mammalian phenotyhpe ontology
  • abnormal learning/memory/conditioning(MP:0002063)

  • abnormal synapse morphology(MP:0009538)

  • amyloid beta deposits(MP:0003329)

  • amyloidosis(MP:0000604)

  • astrocytosis(MP:0003354)
  • more 1 phenotypes
  • microgliosis(MP:0008918)
  • Detailed phenotype data

    Ordering Information

    供与核酸phage P1 loxP site, yeast FRT (flipase recombination target) site, mouse App genomic DNA (mutant type)
    Research applicationCre/loxP system
    FLP/frt system
    Mouse Models for Human Disease
    提供条件条件を付加する。
    本件リソースは国立研究開発法人理化学研究所が所有権を有している。研究成果の公表にあたって斉藤貴志博士、西道隆臣博士への謝辞の表明を必要とする。利用者は、本件リソースを利用して得られた全ての論文発表においては、Nature Neuroscience 17, 661-663 (2014)を引用する。利用者は、本件リソースに関わる全ての口頭発表および出版物において、寄託者に謝辞を述べる。利用者は、本件リソースに関して寄託者から提供された「CONFIDENTIAL」と捺印されたいかなる情報も機密としなくてはならない。口頭での議論も、議論がなされた日から30日以内に文書化されて「CONFIDENTIAL」と捺印された場合は、機密情報とする。営利機関はライセンス契約について寄託者に直接問い合わせる(takaomi.saido@riken.jp)。提供MTAの期間内に、本件リソースを用いた研究計画の遂行において、利用者が発明を創出し実用化した場合は、利用者はこの発明について速やかに寄託者に通知しなくてはならない。また、当事者は特許申請を提出する前に、その発明に対する各当事者の貢献に基づいた発明者適格および所有権を決定するために各々と協議することとする。共同所有の出願の場合には、各当事者は、出願手続きに係る責任について、並びに、所有権、特許費用及び特許料収入の共有について、寄託者と共同出願協定を締結することとする。
    Depositor西道 隆臣(独立行政法人理化学研究所)
    Strain Status生体のアイコン生体
    凍結胚のアイコン凍結胚
    凍結精子のアイコン凍結精子
    Strain Availability凍結精子を1ヶ月以内に提供可能
    凍結胚を1ヶ月以内に提供可能
    生体マウスを1~3ヶ月以内に提供可能
    Additional Info.Necessary documents for ordering:
    1. Order form (Japanese / English)
    2. Category I MTA: MTA for distribution with RIKEN BRC (Japanese / English)
    3. Acceptance of responsibility for living modified organism (Japanese / English)
    Lab HP (Japanese/English)
    Genotyping protocol -PCR-
    Mouse of the Month Sep 2014

    BRC mice in Publications

    Nagashima K, Watanabe H, Akasaka T, Ono M.
    Development of Triphenylmethane Dyes for In Vivo Fluorescence Imaging of Aβ Oligomers.
    ACS Chem Neurosci 15(11) 2233-2242(2024) 38753435
    Xie Z, Meng J, Kong W, Wu Z, Lan F, Narengaowa, Hayashi Y, Yang Q, Bai Z, Nakanishi H, Qing H, Ni J.
    Microglial cathepsin E plays a role in neuroinflammation and amyloid β production in Alzheimer's disease.
    Aging Cell 21(3) e13565(2022) 35181976
    Takebayashi Y, Yamazaki Y, Yamada H, Yazawa K, Nakamori M, Kurashige T, Morino H, Takahashi T, Sotomaru Y, Maruyama H.
    Apolipoprotein E genotype-dependent accumulation of amyloid β in APP-knock-in mouse model of Alzheimer's disease.
    Biochem Biophys Res Commun 683 149106(2023) 37857162
    Yoshiko Takebayashi, Yu Yamazaki, Hidetada Yamada, Kyosuke Yazawa, Masahiro Nakamori, Takashi Kurashige, Hiroyuki Morino, Tetsuya Takahashi, Yusuke Sotomaru, Hirofumi Maruyama
    Apolipoprotein E genotype-dependent accumulation of amyloid β in APP-knock-in mouse model of Alzheimer's disease
    Biochemical and Biophysical Research Communications (2023)
    Ho H, Kejzar N, Sasaguri H, Saito T, Saido TC, De Strooper B, Bauza M, Krupic J.
    A fully automated home cage for long-term continuous phenotyping of mouse cognition and behavior.
    Cell Rep Methods 3(7) 100532(2023) 37533650
    Tomoyuki Mano, Ken Murata, Kazuhiro Kon, Chika Shimizu, Hiroaki Ono, Shoi Shi, Rikuhiro G. Yamada, Kazunari Miyamichi, Etsuo A. Susaki, Kazushige Touhara, Hiroki R. Ueda
    CUBIC-Cloud provides an integrative computational framework toward community-driven whole-mouse-brain mapping
    Cell Reports Methods 1 100038(2021) 35475238
    Liu X, Zhou Q, Zhang JH, Wang KY, Saito T, Saido TC, Wang X, Gao X, Azuma K.
    Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer's Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin.
    Cells 10(11) (2021) 34831483
    Yoshida K, Kato D, Sugio S, Takeda I, Wake H.
    Activity-dependent oligodendrocyte calcium dynamics and their changes in Alzheimer's disease.
    Front Cell Neurosci 17 1154196(2023) 38026691
    Hiroki Sasaguri, Shoko Hashimoto, Naoto Watamura, Kaori Sato, Risa Takamura, Kenichi Nagata, Satoshi Tsubuki, Toshio Ohshima, Atsushi Yoshiki, Kenya Sato, Wakako Kumita, Erika Sasaki, Shinobu Kitazume, Per Nilsson, Bengt Winblad, Takashi Saito, Nobuhisa Iwata, Takaomi C. Saido
    Recent Advances in the Modeling of Alzheimer’s Disease
    Frontiers Neuroscience 16 (2022) 35431779
    Kaneko R, Matsui A, Watanabe M, Harada Y, Kanamori M, Awata N, Kawazoe M, Takao T, Kobayashi Y, Kikutake C, Suyama M, Saito T, Saido TC, Ito M.
    Increased neutrophils in inflammatory bowel disease accelerate the accumulation of amyloid plaques in the mouse model of Alzheimer's disease.
    Inflamm Regen 43(1) 20(2023) 36922861
    Sahu B, Johnson LM, Sohrabi M, Usatii AA, Craig RMJ, Kaelberer JB, Chandrasekaran SP, Kaur H, Nookala S, Combs CK.
    Effects of Probiotics on Colitis-Induced Exacerbation of Alzheimer's Disease in AppNL-G-F Mice.
    Int J Mol Sci 24(14) (2023) 37511312
    Abdelhamid M, Zhou C, Ohno K, Kuhara T, Taslima F, Abdullah M, Jung CG, Michikawa M.
    Probiotic Bifidobacterium breve Prevents Memory Impairment Through the Reduction of Both Amyloid-β Production and Microglia Activation in APP Knock-In Mouse.
    J Alzheimers Dis 85(4) 1555-1571(2022) 34958017
    Akasaka T, Watanabe H, Ono M.
    In Vivo Near-Infrared Fluorescence Imaging Selective for Soluble Amyloid β Aggregates Using y-Shaped BODIPY Derivative.
    J Med Chem (2023) 37824378
    Murakami A, Hara T, Yamada-Kubota C, Kuwahara M, Ichikawa T, Minagi S.
    Lack of occlusal support did not impact amyloid β deposition in APP knock-in mice.
    J Prosthodont Res 66(1) 161-166(2022) 34305086
    Minamisawa M, Sato Y, Ishiguro E, Taniai T, Sakamoto T, Kawai G, Saito T, Saido TC.
    Amelioration of Alzheimer's Disease by Gut-Pancreas-Liver-Brain Interaction in an App Knock-In Mouse Model.
    Life (Basel) 12(1) (2021) 35054427
    Honda K, Saito Y, Saito H, Toyoda M, Abe R, Saito T, Saido TC, Michikawa M, Taru H, Sobu Y, Hata S, Nakaya T, Suzuki T.
    Accumulation of amyloid-β in the brain of mouse models of Alzheimer's disease is modified by altered gene expression in the presence of human apoE isoforms during aging.
    Neurobiol Aging 123 63-74(2023) 36638682
    Ye Q, Gast G, Su X, Saito T, Saido TC, Holmes TC, Xu X.
    Hippocampal neural circuit connectivity alterations in an Alzheimer's disease mouse model revealed by monosynaptic rabies virus tracing.
    Neurobiol Dis 172 105820(2022) 35843448
    Mona Abdelhamid, Cha-Gyun Jung, Chunyu Zhou, Rieko Inoue, Yuxin Chen, Yoshiki Sento, Hideki Hida, Makoto Michikawa
    Potential Therapeutic Effects of Bifidobacterium breve MCC1274 on Alzheimer’s Disease Pathologies in AppNL-G-F Mice
    Nutrients 16 538(2024)
    Fukuda M, Okanishi H, Ino D, Ono K, Kawamura S, Wakai E, Miyoshi T, Sato T, Ohta Y, Saito T, Saido TC, Inohara H, Kanai Y, Hibino H.
    Disturbance in the protein landscape of cochlear perilymph in an Alzheimer's disease mouse model.
    PLoS One 19(5) e0303375(2024) 38728348
    Bellio TA, Laguna-Torres JY, Campion MS, Chou J, Yee S, Blusztajn JK, Mellott TJ.
    Perinatal choline supplementation prevents learning and memory deficits and reduces brain amyloid Aβ42 deposition in AppNL-G-F Alzheimer's disease model mice.
    PLoS One 19(2) e0297289(2024) 38315685
    Yamada H, Yamazaki Y, Takebayashi Y, Yazawa K, Sasanishi M, Motoda A, Nakamori M, Morino H, Takahashi T, Maruyama H.
    The long-term effects of heated tobacco product exposure on the central nervous system in a mouse model of prodromal Alzheimer's disease.
    Sci Rep 14(1) 227(2024) 38167640
    Gannon M, Wang B, Stringfellow SA, Quintin S, Mendoza I, Srikantha T, Roberts AC, Saito T, Saido TC, Roberson ED, Yacoubian TA.
    14-3-3θ Does Not Protect against Behavioral or Pathological Deficits in Alzheimer's Disease Mouse Models.
    eNeuro 9(3) (2022) 35697511