Applications and considerations for the use of genetically engineered mouse models in drug development

Humanized mouse models of immunological diseases and precision medicine

(2019) Leonard D. Shultz et al.   MAMMALIAN GENOME

Genetically engineered pigs as models for human disease

(2018) Carolin Perleberg et al.   Disease Models & Mechanisms

CYP-humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity

(2018) Karl-Dimiter Bissig et al.   DRUG METABOLISM AND DISPOSITION

Gantenerumab: A Novel Human Anti-Aβ Antibody Demonstrates Sustained Cerebral Amyloid-β Binding and Elicits Cell-Mediated Removal of Human Amyloid-β

(2018) Bernd Bohrmann et al.   JOURNAL OF ALZHEIMERS DISEASE

OTULIN limits cell death and inflammation by deubiquitinating LUBAC

(2018) Klaus Heger et al.   NATURE

LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis

(2018) Nieves Peltzer et al.   NATURE

Genome Editing of Pigs for Agriculture and Biomedicine

(2018) Huaqiang Yang et al.   Frontiers in Genetics

Ubiquitin ligase COP1 coordinates transcriptional programs that control cell type specification in the developing mouse brain

(2018) Kim Newton et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Genome Toxicity and Impaired Stem Cell Function after Conditional Activation of CreERT2 in the Intestine

(2018) Natacha Bohin et al.   Stem Cell Reports

Accelerating Biomedical Discoveries through Rigor and Transparency

(2017) Judith A. Hewitt et al.   ILAR JOURNAL

Application of genome editing technologies in rats for human disease models

(2017) Kazuto Yoshimi et al.   JOURNAL OF HUMAN GENETICS

Microbiota and reproducibility of rodent models

(2017) Craig L Franklin et al.   LAB ANIMAL

Krasmutant genetically engineered mouse models of human cancers are genomically heterogeneous

(2017) Wei-Jen Chung et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Reproductive and developmental toxicology studies with gantenerumab in PS2APP transgenic mice

(2017) Paul Barrow et al.   REPRODUCTIVE TOXICOLOGY

Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease

(2017) Claire E. Le Pichon et al.   Science Translational Medicine

Tumour and host cell PD-L1 is required to mediate suppression of anti-tumour immunity in mice

(2017) Janet Lau et al.   Nature Communications

Retinoid-related orphan receptor γ (RORγ) adult induced knockout mice develop lymphoblastic lymphoma

(2016) Maria Liljevald et al.   AUTOIMMUNITY REVIEWS

RIPK3 deficiency or catalytically inactive RIPK1 provides greater benefit than MLKL deficiency in mouse models of inflammation and tissue injury

(2016) K Newton et al.   CELL DEATH AND DIFFERENTIATION

Innovation in the pharmaceutical industry: New estimates of R&D costs

(2016) Joseph A. DiMasi et al.   JOURNAL OF HEALTH ECONOMICS

Preclinical Safety Profile of a Depleting Antibody against CRTh2 for Asthma: Well Tolerated Despite Unexpected CRTh2 Expression on Vascular Pericytes in the Central Nervous System and Gastric Mucosa

(2016) Kathila S. Rajapaksa et al.   TOXICOLOGICAL SCIENCES

Identification of Modifier Genes in a Mouse Model of Gaucher Disease

(2016) Andrés D. Klein et al.   Cell Reports

Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences

(2016) Gillian M. Lavelle et al.   Biomed Research International

Mouse Genome Engineering via CRISPR-Cas9 for Study of Immune Function

(2015) Stephane Pelletier et al.   IMMUNITY

Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer

(2015) Daniel V.T. Catenacci et al.   JOURNAL OF CLINICAL ONCOLOGY

Translational value of mouse models in oncology drug development

(2015) Stephen E Gould et al.   NATURE MEDICINE

Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations

(2015) S. Okada et al.   SCIENCE

Inhibition of the kinase ITK in a mouse model of asthma reduces cell death and fails to inhibit the inflammatory response

(2015) Yonglian Sun et al.   Science Signaling

Effect of selective LRRK2 kinase inhibition on nonhuman primate lung

(2015) Reina N. Fuji et al.   Science Translational Medicine

Regulatory Forum Opinion Piece*

(2015) Abigail C. Jacobs et al.   TOXICOLOGIC PATHOLOGY

Inhibition of the kinase ITK in a mouse model of asthma reduces cell death and fails to inhibit the inflammatory response

(2015) Yonglian Sun et al.   Science Signaling

Antitumor Efficacy of a Bispecific Antibody That Targets HER2 and Activates T Cells

(2014) T. T. Junttila et al.   CANCER RESEARCH

Cutting Edge: RIPK1 Kinase Inactive Mice Are Viable and Protected from TNF-Induced Necroptosis In Vivo

(2014) Apostolos Polykratis et al.   JOURNAL OF IMMUNOLOGY

RIP3 Induces Apoptosis Independent of Pronecrotic Kinase Activity

(2014) Pratyusha Mandal et al.   MOLECULAR CELL

Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework

(2014) David Cook et al.   NATURE REVIEWS DRUG DISCOVERY

Phenotype of Transgenic Mice Carrying a Very Low Copy Number of the Mutant Human G93A Superoxide Dismutase-1 Gene Associated with Amyotrophic Lateral Sclerosis

(2014) Jeffrey S. Deitch et al.   PLoS One

Genomic responses in mouse models greatly mimic human inflammatory diseases

(2014) Keizo Takao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition

(2014) W. J. Kaiser et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Activity of Protein Kinase RIPK3 Determines Whether Cells Die by Necroptosis or Apoptosis

(2014) K. Newton et al.   SCIENCE

Fialuridine Induces Acute Liver Failure in Chimeric TK-NOG Mice: A Model for Detecting Hepatic Drug Toxicity Prior to Human Testing

(2014) Dan Xu et al.   PLOS MEDICINE

One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering

(2013) Haoyi Wang et al.   CELL

Generation of gene-modified mice via Cas9/RNA-mediated gene targeting

(2013) Bin Shen et al.   CELL RESEARCH

The use of genetically modified mice in cancer risk assessment: Challenges and limitations

(2013) David A. Eastmond et al.   CRITICAL REVIEWS IN TOXICOLOGY

Genetically engineered mouse models of pancreatic adenocarcinoma

(2013) Carmen Guerra et al.   Molecular Oncology

Genomic responses in mouse models poorly mimic human inflammatory diseases

(2013) Junhee Seok et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Regulatory Forum Commentary

(2013) Daniel Morton et al.   TOXICOLOGIC PATHOLOGY

Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei

(2013) Kent Fitzgerald et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

IAPs limit activation of RIP kinases by TNF receptor 1 during development

(2012) Maryline Moulin et al.   EMBO JOURNAL

GLP-1 Receptor Agonists and the Thyroid: C-Cell Effects in Mice Are Mediated via the GLP-1 Receptor and not Associated with RET Activation

(2012) Lars Wichmann Madsen et al.   ENDOCRINOLOGY

Raise standards for preclinical cancer research

(2012) C. Glenn Begley et al.   NATURE

Loss of the Tumor Suppressor BAP1 Causes Myeloid Transformation

(2012) A. Dey et al.   SCIENCE

A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity

(2012) M. Jinek et al.   SCIENCE

Nonclinical safety strategies for stem cell therapies

(2012) Michaela E. Sharpe et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

Zebrafish Models for Human Cancer

(2012) H. R. Shive   VETERINARY PATHOLOGY

Supporting conditional mouse mutagenesis with a comprehensive cre characterization resource

(2012) Caleb S. Heffner et al.   Nature Communications

Prostate Epithelial Pten/TP53 Loss Leads to Transformation of Multipotential Progenitors and Epithelial to Mesenchymal Transition

(2011) Philip Martin et al.   AMERICAN JOURNAL OF PATHOLOGY

A knockout mouse resource for the biomedical research community

(2011) K. C. Kent Lloyd   Annals of the New York Academy of Sciences

Assessing the Safety of Stem Cell Therapeutics

(2011) Chris E.P. Goldring et al.   Cell Stem Cell

Mouse models of cystic fibrosis: Phenotypic analysis and research applications

(2011) Martina Wilke et al.   Journal of Cystic Fibrosis

Robust Central Reduction of Amyloid-  in Humans with an Orally Available, Non-Peptidic  -Secretase Inhibitor

(2011) P. C. May et al.   JOURNAL OF NEUROSCIENCE

Believe it or not: how much can we rely on published data on potential drug targets?

(2011) Florian Prinz et al.   NATURE REVIEWS DRUG DISCOVERY

Transgenic Animal Models in Toxicology: Historical Perspectives and Future Outlook

(2011) Darrell R. Boverhof et al.   TOXICOLOGICAL SCIENCES

A Critical Review of the Effectiveness of Rodent Pharmaceutical Carcinogenesis Testing in Predicting for Human Risk

(2011) C. L. Alden et al.   VETERINARY PATHOLOGY

Virus-Plus-Susceptibility Gene Interaction Determines Crohn's Disease Gene Atg16L1 Phenotypes in Intestine

(2010) Ken Cadwell et al.   CELL

Assessing therapeutic responses in Kras mutant cancers using genetically engineered mouse models

(2010) Mallika Singh et al.   NATURE BIOTECHNOLOGY

Tamoxifen-Independent Recombination in the RIP-CreER Mouse

(2010) Yanmei Liu et al.   PLoS One

Carcinogenicity Assessments of Biotechnology-Derived Pharmaceuticals

(2010) John L. Vahle et al.   TOXICOLOGIC PATHOLOGY

Direct Hematological Toxicity and Illegitimate Chromosomal Recombination Caused by the Systemic Activation of CreERT2

(2009) A. Y. Higashi et al.   JOURNAL OF IMMUNOLOGY

Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer

(2009) K. P. Olive et al.   SCIENCE

An Industry Perspective on the Utility of Short-Term Carcinogenicity Testing in Transgenic Mice in Pharmaceutical Development

(2009) Richard D. Storer et al.   TOXICOLOGIC PATHOLOGY

Species selection considerations for preclinical toxicology studies for biotherapeutics

(2008) Jeanine L Bussiere   Expert Opinion on Drug Metabolism & Toxicology

A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells

(2008) Ken Cadwell et al.   NATURE