Humanized Knockin Mouse Models
Get supplemental information, a quote, and estimated timeframe for generating your humanized Knockin mouse. |
A humanized Knockin mouse defines a model in which a mouse gene is replaced by either a human gene, genomic sequence or regulatory element.
This substitution can target parts of the gene, and subsequently specific domains of the protein, as well as certain mouse regulatory elements such as the promoter.
The human protein/domain is then expressed in cells and tissues where the mouse protein was expressed.
Typical applications for humanized Knockin mouse models
For academic research:
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For bio-pharmaceutical research & development:
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Strengths and limitations of humanized Knockin mouse models
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- Physiological expression patterns due to the murine promoter and regulatory elements
- Murine gene is inactivated; no hybrid sequences (like, e.g., in transgenic animals)
- Combination with access to Knockout model for specificity studies
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- Risk of differential expression in mouse vs. human, due to differences in protein regulation
- Low conservation between human/mouse protein => risk of hypomorphism up to protein Knockout
→ Limitation can be bypassed by using chimeric molecules to improve functionality in mouse cells
Case studies and publications on our humanized Knockin mouse models
Case studies
Case 1 | Study of a human-specific receptor
Schwarz F, et al. Paired Siglec receptors generate opposite inflammatory responses to a human-specific pathogen. EMBO J. 2017.
E. coli K1 is a human-specific pathogen that appears to exploit a receptor Siglec-11 expressed only in the human brain.
Mice do not have paired Siglec receptors.
Model: Mice expressing a chimeric, human-type paired Siglec receptor E16.
Aim: To demonstrate that activating Siglecs confer better protection against bacterial infection in vivo.
Results: Siglec-E16 was able to produce protective inflammatory responses to bacterial infection.
Figure 1. Schematic representation of Siglec-E and Siglec-E16 receptors.
The parts of Siglec-E16 derived from mouse Siglec-E or human Siglec-16 are drawn in gray and black, respectively.
Figure 2. Activating Siglecs confer protection against E. coli K1 challenge.
A) Decreased E. coli survival in blood from E16/E16 mice, 1 hour after infection.
B) Less recovered bacteria from blood, spleen, and liver from E16/E16 mice.
C) Increased cytokine levels in serum from E16/E16 mice, 1 hour after bacterial challenge.
Case 2 | Biomarker identification in a rare disease ALD model
van de Beek MC, et al. C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man. PLoS One. 2016.
X-linked adrenoleukodystrophy, ALD, is a progressive neurodegenerative disease, and a result of very-long-chain fatty acid (VLCFA) buildup caused by relevant enzymes not functioning properly (mutations in Abcd1).
Model: Abcd1 Knockout overexpressing human Evolv1, an essential enzyme in the elongation of VLCFA (C22:0 to C26:0).
Aim: To develop an ALD model with increased VLCFA (>C22) levels in the central nervous system for the identification of new biomarkers for ALD.
Results: The VLCFA C26:0-Carnitine is a new biomarker for ALD that reflects elevated VLCFA levels present in the central nervous system of mice and humans.
Figure 1. C26:0-carnitine is highly elevated in central nervous tissue.
C26:0-carnitine levels in brain and spinal cord from wildtype (n=6), Abcd1y/- knockout (n=6) and Abcd1y/-;Cnp-ELOVL1+/- (n=6) mice.
Figure 2. C26:0-carnitine is highly elevated in mouse and human bloodspots.
Left) Bloodspot C26:0-carnitine in wildtype (n=8), Abcd1y/- knockout (n=10) and Abcd1y/-;Cnp-ELOVL1+/- (n=6) mice.
Right) Bloodspot C26:0-carnitine in controls (n=23) and ALD patients (n=10).
Case 3 | Functional validation of an antibody against GPCR
Butcher AJ, et al. An Antibody Biosensor Establishes the Activation of the M1 Muscarinic Acetylcholine Receptor during Learning and Memory. J Biol Chem. 2016.
Establishing the in vivo activation status of G protein-coupled receptors (GPCRs) would not only indicate physiological roles of GPCRs but would also aid drug discovery by establishing drug-receptor engagement.
Model: Mice expressing a humanized, mutated form of the GPCR M1mAChR.
Aim: To develop a phospho-specific antibody-based biosensor to detect activation of the M1 muscarinic acetylcholine receptor in vitro and in vivo.
Results: Phosphorylation sites can be used to probe the activation status of GPCRs during physiological responses and on drug treatment.
Figure 1. Detection of phosphorylation of M1 DREADD receptor in the hippocampus following receptor activation with a selective agonist.
A) Illustration of M1 DREADD receptor. Two point mutations were introduced into the human M1 mAChR, abolishing the activation by ACh, but instead the receptor could be activated by the drug CNO.
B) Fixed sections from M1 mAChRKO mice (M1-KO) or M1 DREADD KI mice treated with vehicle or CNO were co-stained with anti-HA (green) and anti phospho-specific antibodies (red).
The arrows indicate two neurons, where the staining for the receptor and the phosphorylated receptor occur in the same neuron.
The areas marked by the white box are magnified in the lower panels.
Case 4 | Human disease model for acute myeloid leukemia (AML)
Sportoletti P, et al. The human NPM1 mutation A perturbs megakaryopoiesis in a conditional mouse model. Blood. 2013.
The NPM1 mutation is a frequent genetic alteration in acute myeloid leukemia (AML). Despite progress in the clinical and biological characterization of NPM1-mutated AML, the role of NPM1 mutation in leukemogenesis in vivo has not been fully elucidated.
Model: Mice that conditionally express the most common human NPM1 mutation (type A) in the hematopoietic compartment.
Aim: To develop an AML model to identify the role of NPM1 in leukemogenesis.
Results: The NPM1 mutant affects megakaryocytic development in mice and mimics some features of human NPM1-mutated AML.
Figure 1. Immature megakariocytes were increased 2-fold in heterozygous (Npm1-TCTG/WT;Cre1) and 4-fold in homozygous (Npm1-TCTG/TCTG;Cre1) mutant mice.
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B) Quantification of CD411 megakaryocytic cells in the BM of age-matched mutant mice analyzed as in panel A. |
Figure 2. Perturbation in megakaryocyte growth shown in in vitro colony-forming assays.
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Publications
Chiahsuan Chin, Ranjithkumar Ravichandran, Kristina Sanborn, Timothy Fleming, Stephen B Wheatcroft, Mark T Kearney, Sofya Tokman, Rajat Walia, Michael A Smith, David J Flint, Thalachallour Mohanakumar, Ross M Bremner, Angara Sureshbabu.
Loss of IGFBP2 mediates alveolar type 2 cell senescence and promotes lung fibrosis.
Cell Rep Med. 2023 Feb 9
Christoph Hudemann, Yvonne Exner, Robert Pollmann, Karina Schneider, Anna Zakrzewicz, Simon Feldhoff, Thomas Schmidt, Volker Spindler, David Rafei-Shamsabadi, Frauke Völlner, Jens Waschke, Ritva Tikkanen, Michael Hertl, Rüdiger Eming.
IgG against the Membrane-Proximal Portion of the Desmoglein 3 Ectodomain Induces Loss of Keratinocyte Adhesion, a Hallmark in Pemphigus Vulgaris.
J Invest Dermatol. 2023 Feb
Karianne Fjeld, Anny Gravdal, Ranveig S Brekke, Jahedul Alam, Steven J Wilhelm, Khadija El Jellas, Helene N Pettersen, Jianguo Lin, Marie H Solheim, Solrun J Steine, Bente B Johansson, Pål R Njølstad, Caroline S Verbeke, Xunjun Xiao, Mark E Lowe, Anders Molven.
The genetic risk factor CEL-HYB1 causes proteotoxicity and chronic pancreatitis in mice.
Pancreatology. 2022 Dec
Frédéric Adam, Alexandre Kauskot, Lamia Lamrani, Jean Solarz, Christelle Soukaseum, Christelle Repérant, Cécile V Denis, Hana Raslova, Jean-Philippe Rosa, Marijke Bryckaert.
A gain-of-function filamin A mutation in mouse platelets induces thrombus instability.
J Thromb Haemost. 2022 Nov
Julia Leschik, Antonietta Gentile, Cigdem Cicek, Sophie Péron, Margaryta Tevosian, Annika Beer, Konstantin Radyushkin, Anna Bludau, Karl Ebner, Inga Neumann, Nicolas Singewald, Benedikt Berninger, Volkmar Lessmann, Beat Lutz.
Brain-derived neurotrophic factor expression in serotonergic neurons improves stress resilience and promotes adult hippocampal neurogenesis
Prog Neurobiol. 2022 Jul 21
Lai Wen, Alex Marki, Zhihao Wang, Marco Orecchioni, Jeffrey Makings, Monica Billitti, Erpei Wang, Sujit S A Suthahar, Kenneth Kim, William B Kiosses, Zbigniew Mikulski, Klaus Ley.
A humanized β 2 integrin knockin mouse reveals localized intra- and extravascular neutrophil integrin activation in vivo.
Cell Rep. 2022 May 31
Francesca Mateo, Zhengcheng He, Lin Mei, Gorka Ruiz de Garibay, Carmen Herranz, Nadia García, Amanda Lorentzian, Alexandra Baiges, Eline Blommaert, Antonio Gómez, Oriol Mirallas, Anna Garrido-Utrilla, Luis Palomero, Roderic Espín, Ana I Extremera, M Teresa Soler-Monsó, Anna Petit, Rong Li, Joan Brunet, Ke Chen, Susanna Tan, Connie J Eaves, Curtis McCloskey, Razq Hakem, Rama Khokha, Philipp F Lange, Conxi Lázaro, Christopher A Maxwell, Miquel Angel Pujana.
Modification of BRCA1-associated breast cancer risk by HMMR overexpression.
Nat Commun. 2022 Apr 7
Álvaro Sebastián-Serrano, Jesús Merchán-Rubira, Caterina Di Lauro, Carolina Bianchi, Lucía Soria-Tobar, Sonoko Narisawa, José L Millán, Jesús Ávila, Félix Hernández, Miguel Díaz-Hernández.
TNAP upregulation is a critical factor in Tauopathies and its blockade ameliorates neurotoxicity and increases life-expectancy
Neurobiol Dis. 2022 Apr
Isabel Fernández-Pisonero, Laura Clavaín, Javier Robles-Valero, L Francisco Lorenzo-Martín, Rubén Caloto, Blanca Nieto, Carmen García-Macías, Clara L Oeste, Manuel Sánchez-Martín, Antonio Abad, Alejandro Hortal, Dolores Caballero, Marcos González, Mercedes Dosil, Balbino Alarcón, Xosé R Bustelo.
A hotspot mutation targeting the R-RAS2 GTPase acts as a potent oncogenic driver in a wide spectrum of tumors.
Cell Rep. 2022 Mar 15
Sarah Chan, Nicole Belmar, Sun Ho, Bryan Rogers, Marcia Stickler, Michelle Graham, Eileen Lee, Ninian Tran, Dong Zhang, Priyanka Gupta, Mien Sho, Tracy MacDonough, Andrew Woolley, Han Kim, Hong Zhang, Wei Liu, Pingping Zheng, Zoltan Dezso, Kyle Halliwill, Michele Ceccarelli, Susan Rhodes, Archana Thakur, Charles M Forsyth, Mengli Xiong, Siu Sze Tan, Ramesh Iyer, Marc Lake, Enrico Digiammarino, Li Zhou, Lance Bigelow, Kenton Longenecker, Russell A Judge, Cassie Liu, Max Trumble, Jonathan P Remis, Melvin Fox, Belinda Cairns, Yoshiko Akamatsu, Diane Hollenbaugh, Fiona Harding, Hamsell M Alvarez.
An anti-PD-1-GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy
Nat Cancer. 2022 Mar 7
Julie A Zorn, Matthew L Wheeler, Ralston M Barnes, Jim Kaberna, Winse Morishige, Marek Harris, Richard Y-C Huang, Jack Lohre, Yu Ching Chang, Bryant Chau, Kathleen Powers, Ian Schindler, Naveen Neradugomma, Winston Thomas, Xiaoyun Liao, Yinhan Zhou, Sean M West, Feng Wang, Srikanth Kotapati, Guodong Chen, Sayumi Yamazoe, Anastasia Kosenko, Gavin Dollinger, Tim Sproul, Arvind Rajpal, Pavel Strop.
Humanization of a strategic CD3 epitope enables evaluation of clinical T-cell engagers in a fully immunocompetent in vivo model
Sci Rep. 2022 Mar 3
Alejandro M Hortal, Clara L Oeste, Claudia Cifuentes, Miguel Alcoceba, Isabel Fernández-Pisonero, Laura Clavaín, Rut Tercero, Pilar Mendoza, Verónica Domínguez, Marta García-Flores, Belén Pintado, David Abia, Carmen García-Macías, Almudena Navarro-Bailón, Xosé R Bustelo, Marcos González, Balbino Alarcón.
Overexpression of wild type RRAS2, without oncogenic mutations, drives chronic lymphocytic leukemia
Mol Cancer. 2022 Feb 4
Alexandre Bacq, Delphine Roussel, Thomas Bonduelle, Sara Zagaglia, Marina Maletic, Théo Ribierre, Homa Adle-Biassette, Cécile Marchal, Mélanie Jennesson, Isabelle An, Genomics England Research Consortium; Fabienne Picard, Vincent Navarro, Sanjay M Sisodiya, Stéphanie Baulac.
Cardiac Investigations in Sudden Unexpected Death in DEPDC5-Related Epilepsy
Ann Neurol. 2022 Jan
Bjoern Traenkle, Philipp D Kaiser, Stefania Pezzana, Jennifer Richardson, Marius Gramlich, Teresa R Wagner, Dominik Seyfried, Melissa Weldle, Stefanie Holz, Yana Parfyonova, Stefan Nueske, Armin M Scholz, Anne Zeck, Meike Jakobi, Nicole Schneiderhan-Marra, Martin Schaller, Andreas Maurer, Cécile Gouttefangeas, Manfred Kneilling, Bernd J Pichler, Dominik Sonanini, Ulrich Rothbauer
Single-Domain Antibodies for Targeting, Detection, and In Vivo Imaging of Human CD4 + Cells
Front Immunol. 2021 Dec 9
Li-Chiung Lin, Tezz Quon, Susanna Engberg, Amanda E Mackenzie, Andrew B Tobin, Graeme Milligan
G Protein-Coupled Receptor GPR35 Suppresses Lipid Accumulation in Hepatocytes.
ACS Pharmacol Transl Sci. 2021 Nov 30
Aditi R Saxena, Donal N Gorman, Ryan M Esquejo, Arthur Bergman, Kristin Chidsey, Clare Buckeridge, David A Griffith, Albert M Kim.
Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial.
Nat Med. 2021 Jun
Faik Imeri, Bisera Stepanovska Tanturovska, Stephanie Schwalm, Sarbari Saha, Jinyang Zeng-Brouwers, Herrmann Pavenstädt, Josef Pfeilschifter, Liliana Schaefer, Andrea Huwiler.
Loss of sphingosine kinase 2 enhances Wilm's tumor suppressor gene 1 and nephrin expression in podocytes and protects from streptozotocin-induced podocytopathy and albuminuria in mice.
Matrix Biol. 2021 Apr
Talat H Malik, Daniel P Gitterman 2, Deborah P Lavin, Hannah J Lomax-Browne, E Christina Hiemeyer, Linda B Moran, Katharina Boroviak, H Terence Cook, Alyssa C Gilmore, Mawj Mandwie, Amina Ahmad, Ian E Alexander, Grant J Logan, Kevin J Marchbank, Allan Bradley, Matthew C Pickering.
Gain-of-function factor H-related 5 protein impairs glomerular complement regulation resulting in kidney damage.
Proc Natl Acad Sci U S A. 2021 Mar 30
Anastasia Noël, Bénédicte Foveau, Andréa C LeBlanc.
Caspase-6-cleaved Tau fails to induce Tau hyperphosphorylation and aggregation, neurodegeneration, glial inflammation, and cognitive deficits.
Cell Death Dis. 2021 Mar 1
Julien C Vantourout, Andrew M Mason, Josephine Yuen, Graham L Simpson, Ghotas Evindar, Letian Kuai, Michael Hobbs, Emma Edgar, Saul Needle, Xiaopeng Bai, Steve Wilson, Paul Scott-Stevens, William Traylen, Kim Lambert, Neil Young, Shenaz Bunally, Scott G Summerfield, Richard Snell, Rakesh Lad, Eric Shi, Steven Skinner, Lisa Shewchuk, Allan J B Watson, Chun-Wa Chung, Sandeep Pal, Dennis A Holt, Lara S Kallander, Joanne Prendergast, Katrina Rivera, David G Washburn, Mark R Harpel, Christopher Arico-Muendel, Albert Isidro-Llobet.
In Vivo Half-Life Extension of BMP1/TLL Metalloproteinase Inhibitors Using Small-Molecule Human Serum Albumin Binders.
Bioconjug Chem. 2021 Feb 17
Flavia Amadeu de Oliveira, Sonoko Narisawa, Massimo Bottini, José Luis Millán.
Visualization of Mineral-Targeted Alkaline Phosphatase Binding to Sites of Calcification In Vivo.
J Bone Miner Res. 2020 Apr 28.
Sophie J Bradley, Colin Molloy, Paulina Valuskova, Louis Dwomoh, Miriam Scarpa, Mario Rossi, Lisa Finlayson, Kjell A Svensson, Eyassu Chernet, Vanessa N Barth, Karolina Gherbi, David A Sykes, Caroline A Wilson, Rajendra Mistry, Patrick M Sexton, Arthur Christopoulos, Adrian J Mogg, Elizabeth M Rosethorne, Shuzo Sakata, R A John Challiss, Lisa M Broad, Andrew B Tobin.
Biased M1-muscarinic-receptor-mutant Mice Inform the Design of Next-Generation Drugs.
Nat Chem Biol. 2020 Mar.
ElTanbouly MA, Zhao Y, Nowak E, Li J, Schaafsma E, Le Mercier I, Ceeraz S, Lines JL, Peng C, Carriere C, Huang X, Day M, Koehn B, Lee SW, Silva Morales M, Hogquist KA, Jameson SC, Mueller D, Rothstein J, Blazar BR, Cheng C, Noelle RJ.
VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance.
Science. 2020 Jan 17.
Johnston RJ, Su LJ, Pinckney J, Critton D, Boyer E, Krishnakumar A, Corbett M, Rankin AL, Dibella R, Campbell L, Martin GH, Lemar H, Cayton T, Huang RY, Deng X, Nayeem A, Chen H, Ergel B, Rizzo JM, Yamniuk AP, Dutta S, Ngo J, Shorts AO, Ramakrishnan R, Kozhich A, Holloway J, Fang H, Wang YK, Yang Z, Thiam K, Rakestraw G, Rajpal A, Sheppard P, Quigley M, Bahjat KS, Korman AJ.
VISTA is an acidic pH-selective ligand for PSGL-1.
Nature. 2019 Oct.
Dvela-Levitt M, Kost-Alimova M, Emani M, Kohnert E, Thompson R, Sidhom EH, Rivadeneira A, Sahakian N, Roignot J, Papagregoriou G, Montesinos MS, Clark AR, McKinney D, Gutierrez J, Roth M, Ronco L, Elonga E, Carter TA, Gnirke A, Melanson M, Hartland K, Wieder N, Hsu JC, Deltas C, Hughey R, Bleyer AJ, Kmoch S, Živná M, Barešova V, Kota S, Schlondorff J, Heiman M, Alper SL, Wagner F, Weins A, Golub TR, Lander ES, Greka A.
Small Molecule Targets TMED9 and Promotes Lysosomal Degradation to Reverse Proteinopathy.
Cell. 2019 Jul 25.
Daniele Bolognini, Natasja Barki, Adrian J Butcher, Brian D Hudson, Eugenia Sergeev, Colin Molloy, Catherine E Moss, Sophie J Bradley, Christian Le Gouill, Michel Bouvier, Andrew B Tobin, Graeme Milligan.
Chemogenetics defines receptor-mediated functions of short chain free fatty acids.
Nat Chem Biol. 2019 May.
Kvarnhammar AM, Veitonmäki N, Hägerbrand K, Dahlman A, Smith KE, Fritzell S, von Schantz L, Thagesson M, Werchau D, Smedenfors K, Johansson M, Rosén A, Åberg I, Winnerstam M, Nyblom E, Barchan K, Furebring C, Norlén P, Ellmark P.
The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation.
J Immunother Cancer. 2019 Apr 11.
Reiss J.
Molybdenum cofactor deficiency type B knock-in mouse models carrying patient-identical mutations and their rescue by singular AAV injections.
Hum Genet. 2019 Feb 27.
Elliott M, Favre-Guilmard C, Liu SM, Maignel J, Masuyer G, Beard M, Boone C, Carré D, Kalinichev M, Lezmi S, Mir I, Nicoleau C, Palan S, Perier C, Raban E, Zhang S, Dong M, Stenmark P, Krupp J.
Engineered botulinum neurotoxin B with improved binding to human receptors has enhanced efficacy in preclinical models.
Sci Adv. 2019 Jan 16.
Plucińska K, Crouch B, Yeap JM, Stoppelkamp S, Riedel G, Platt B.
Histological and Behavioral Phenotypes of a Novel Mutated APP Knock-In Mouse.
J Alzheimers Dis. 2018 Aug 7.
Beyer S, Schwalm S, Pfeilschifter J, Huwiler A.
Renal Mesangial Cells Isolated from Sphingosine Kinase 2 Transgenic Mice Show Reduced Proliferation and are More Sensitive to Stress-Induced Apoptosis.
Cell Physiol Biochem. 2018 Jul 10.
Romanelli F, Corbo A, Salehi M, Yadav MC, Salman S, Petrosian D, Rashidbaigi OJ, Chait J, Kuruvilla J, Plummer M, Radichev I, Margulies KB, Gerdes AM, Pinkerton AB, Millán JL, Savinov AY, Savinova OV.
Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia.
PLoS One. 2017 Oct 12.
Schwarz F, Landig CS, Siddiqui S, Secundino I, Olson J, Varki N, Nizet V, Varki A.
Paired Siglec receptors generate opposite inflammatory responses to a human-specific pathogen.
EMBO J. 2017 Jan 18.
Viswambharan H, Yuldasheva NY, Sengupta A, Imrie H, Gage MC, Haywood NJ, Walker AM, Skromna A, Makova N, Galloway SL, Shah P, Sukumar P, Porter KE, Grant PJ, Shah AM, Santos CX, Li J, Beech DJ, Wheatcroft S, Cubbon RM, Kearney MT.
Selective Enhancement of Insulin Sensitivity in the Endothelium In Vivo Reveals a Novel Proatherosclerotic Signalling Loop.
Circ Res. 2016 Dec 5.
Bondulich MK, Guo T, Meehan C, Manion J, Rodriguez Martin T, Mitchell JC, Hortobagyi T, Yankova N, Stygelbout V, Brion JP, Noble W, Hanger DP.
Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate.
Brain. 2016 Jun 12.
van de Beek MC, Dijkstra IM, van Lenthe H, Ofman R, Goldhaber-Pasillas D, Schauer N, Schackmann M, Engelen-Lee JY, Vaz FM, Kulik W, Wanders RJ, Engelen M, Kemp S.
C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man.
PLoS One. 2016 Apr 28.
Butcher AJ, Bradley SJ, Prihandoko R, Brooke SM, Mogg A, Bourgognon JM, Macedo-Hatch T, Edwards JM, Bottrill AR, Challiss RA, Broad LM, Felder CC, Tobin AB.
An antibody biosensor establishes the activation of the M1 muscarinic acetylcholine receptor during learning and memory.
J Biol Chem. 2016 Jan 29.
Savinov AY, Salehi M, Yadav MC, Radichev I, Millán JL, Savinova OV.
Transgenic Overexpression of Tissue-Nonspecific Alkaline Phosphatase (TNAP) in Vascular Endothelium Results in Generalized Arterial Calcification.
J Am Heart Assoc. 2015 Dec 16.
Sheen CR, Kuss P, Narisawa S, Yadav MC, Nigro J, Wang W, Chhea TN, Sergienko EA, Kapoor K, Jackson MR, Hoylaerts MF, Pinkerton AB, O'Neill WC, Millán JL.
Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification.
J Bone Miner Res. 2015 May.
Chen J, Kaiyala KJ, Lam J, Agrawal N, Nguyen L, Ogimoto K, Spencer D, Morton GJ, Schwartz MW, Dichek HL.
In vivo structure-function studies of human hepatic lipase: the catalytic function rescues the lean phenotype of HL-deficient (hl-/-) mice.
Physiol Rep. 2015 Apr 3.
Iqbal AJ, McNeill E, Kapellos TS, Regan-Komito D, Norman S, Burd S, Smart N, Machemer DE, Stylianou E, McShane H, Channon KM, Chawla A, Greaves DR
Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo.
Blood. 2014 Oct 9.
Plucińska K, Crouch B, Koss D, Robinson L, Siebrecht M, Riedel G, Platt B
Knock-in of human BACE1 cleaves murine APP and reiterates Alzheimer-like phenotypes.
J Neurosci. 2014 Aug 6.
LeBlanc AC, Ramcharitar J, Afonso V, Hamel E, Bennett DA, Pakavathkumar P, Albrecht S
Caspase-6 activity in the CA1 region of the hippocampus induces age-dependent memory impairment.
Cell Death Differ. 2014 May 21.
Garanto A, van Beersum SE, Peters TA, Roepman R, Cremers FP, Collin RW.
Unexpected CEP290 mRNA Splicing in a Humanized Knock-In Mouse Model for Leber Congenital Amaurosis.
PLoS One. 2013 Nov 6.
Sportoletti P, Varasano E, Rossi R, Bereshchenko O, Cecchini D, Gionfriddo I, Bolli N, Tiacci E, Intermesoli T, Zanghì P, Masciulli A, Martelli MP, Falzetti F, Martelli MF, Falini B.
The human NPM1 mutation A perturbs megakaryopoiesis in a conditional mouse model.
Blood. 2013 Apr 25.
Ryan D, Koss D, Porcu E, Woodcock H, Robinson L, Platt B, Riedel G.
Spatial learning impairments in PLB1Triple knock-in Alzheimer mice are task-specific and age-dependent.
Cell Mol Life Sci. 2013 Mar 28.
Imrie H, Viswambharan H, Sukumar P, Abbas A, Cubbon RM, Yuldasheva N, Gage M, Smith J, Galloway S, Skromna A, Rashid ST, Futers TS, Xuan S, Gatenby VK, Grant PJ, Channon KM, Beech DJ, Wheatcroft SB, Kearney MT.
Novel role of the IGF-1 receptor in endothelial function and repair: studies in endothelium-targeted IGF-1 receptor transgenic mice.
Diabetes. 2012 Sep.
Platt B, Drever B, Koss D, Stoppelkamp S, Jyoti A, Plano A, Utan A, Merrick G, Ryan D, Melis V, Wan H, Mingarelli M, Porcu E, Scrocchi L, Welch A, Riedel G.
Abnormal Cognition, Sleep, EEG and Brain Metabolism in a Novel Knock-In Alzheimer Mouse, PLB1.
PLoS One. 2011 Nov 11.
Needham LA, Davidson AH, Bawden LJ, Belfield A, Bone EA, Brotherton DH, Bryant S, Charlton MH, Clark VL, Davies SJ, Donald A, Day FA, Krige D, Legris V, McDermott J, McGovern Y, Owen J, Patel SR, Pintat S, Testar RJ, Wells GM, Moffat D, Drummond AH.
Drug targeting to monocytes and macrophages using esterase-sensitive chemical motifs.
J Pharmacol Exp Ther. 2011 Oct.
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