Neuron-Specific Genome Modification in the Adult Rat Brain Using CRISPR-Cas9 Transgenic Rats

Bäck, Susanne; Necarsulmer, Julie; Whitaker, Leslie R.; Coke, Lamarque M.; Koivula, Pyry; Heathward, Emily J.; Fortuno, Lowella V.; Zhang, Yajun; Yeh, Cy.; Baldwin, Heather A.; Spencer, Morgan D.; Mejías-Aponte, Carlos A.; Pickel, James; Hoffman, Alexander F.; Spivak, Charles E.; Lupica, Carl R.; Underhill, Suzanne M.; Amara, Susan G.; Domanskyi, Andrii; Anttila, Jenni E.; Airavaara, Mikko; Hope, Bruce T.; Hamra, F. Kent; Richie, Christopher T.; Harvey, Brandon K.

doi:10.1016/j.neuron.2019.01.035

Cited by 79 publications

(75 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, CRISPR/Cas9 technology allows development of genetically modified rodents in only 2 months with greater predictability, and the ability to modify genes in zygotes makes it feasible to use rats for such studies. Already, genetically modified rats are being used in studies of neurophysiology and cardiovascular disease [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Low-density Lipoprotein Receptor-related Protein 5 (LRP5)-deficient Rats Have Reduced Bone Mass and Abnormal Development of the Retinal Vasculature

Ubels

Diegel

Foxa

et al. 2020

Preprint

View full text Add to dashboard Cite

Humans carrying homozygous loss-of-function mutations in the Wnt co-receptor LRP5 (low-density lipoprotein receptor-related protein 5) develop osteoporosis and a defective retinal vasculature known as familial exudative vitreoretinopathy (FEVR) due to disruption of the Wnt signaling pathway. The purpose of this study was to use CRISPR/Cas9-mediated gene editing to create strains of Lrp5-deficient rats and to determine whether knockout of Lrp5 resulted in phenotypes that model the bone and retina pathology in LRP5-deficient humans. Knockout of Lrp5 in rats produced low bone mass, decreased bone mineral density, and decreased bone size. The superficial retinal vasculature of Lrp5-deficient rats was sparse and disorganized, with extensive exudates and decreases in vascularized area, vessel length, and branch point density.This study showed that Lrp5 could be predictably knocked out in rats using CRISPR/Cas9, causing the expression of bone and retinal phenotypes that will be useful for studying the role of Wnt signaling in bone and retina development and for research on the treatment of osteoporosis and FEVR.

show abstract

Section: Introductionmentioning

confidence: 99%

Low-density Lipoprotein Receptor-related Protein 5 (LRP5)-deficient Rats Have Reduced Bone Mass and Abnormal Development of the Retinal Vasculature

Ubels

Diegel

Foxa

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…As for rats, the Harvey group generated a Parkinson's disease model by knocking out Tyrosine Hydroxylase (TH) gene from brain dopaminergic neurons in rats via intracranial injection of AAV vectors expressing SpCas9 and gRNA (Back et al 2019). This Parkinson's disease rat model is expected to be used for multipurpose studies aimed at developing therapies for this disease.…”

Section: Mice and Ratsmentioning

confidence: 99%

Genome editing methods in animal models

Lee

Yoon

Kim

2020

Animal Cells and Systems

View full text Add to dashboard Cite

Genetically engineered animal models that reproduce human diseases are very important for the pathological study of various conditions. The development of the clustered regularly interspaced short palindromic repeats (CRISPR) system has enabled a faster and cheaper production of animal models compared with traditional gene-targeting methods using embryonic stem cells. Genome editing tools based on the CRISPR-Cas9 system are a breakthrough technology that allows the precise introduction of mutations at the target DNA sequences. In particular, this accelerated the creation of animal models, and greatly contributed to the research that utilized them. In this review, we introduce various strategies based on the CRISPR-Cas9 system for building animal models of human diseases and describe various in vivo delivery methods of CRISPR-Cas9 that are applied to disease models for therapeutic purposes. In addition, we summarize the currently available animal models of human diseases that were generated using the CRISPR-Cas9 system and discuss future directions. ARTICLE HISTORY

show abstract

“…Germline genome editing with CRISPR-Cas9 has emerged as a highly efficient method for producing transgenic strains. As such, CRISPR-Cas9 was used to generate transgenic Cre-dependent Cas9 and Cre-dependent Cas9-nickase [Cas9(D10A)] rats and an improved Cre recombinase (iCre) rat line regulated by the dopamine transporter promoter (DAT-iCre) (Bäck et al, 2019). To show that gene targeting was Cre dependent, Back and coworkers infused AAVs encoding iCre and tyrosine hydroxylase (TH)targeting sgRNAs into the midbrain.…”

Section: Germline Editing With Crisprmentioning

confidence: 99%

Genetically Engineering the Nervous System with CRISPR-Cas

Sandoval

Elahi

Ploski

2020

eNeuro

View full text Add to dashboard Cite

The multitude of neuronal subtypes and extensive interconnectivity of the mammalian brain presents a substantial challenge to those seeking to decipher its functions. While the molecular mechanisms of several neuronal functions remain poorly characterized, advances in next-generation sequencing (NGS) and gene-editing technology have begun to close this gap. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (CRISPR-Cas) system has emerged as a powerful genetic tool capable of manipulating the genome of essentially any organism and cell type. This technology has advanced our understanding of complex neurologic diseases by enabling the rapid generation of novel, disease-relevant in vitro and transgenic animal models. In this review, we discuss recent developments in the rapidly accelerating field of CRISPR-mediated genome engineering. We begin with an overview of the canonical function of the CRISPR platform, followed by a functional review of its many adaptations, with an emphasis on its applications for

show abstract

Neuron-Specific Genome Modification in the Adult Rat Brain Using CRISPR-Cas9 Transgenic Rats

Cited by 79 publications

References 60 publications

Low-density Lipoprotein Receptor-related Protein 5 (LRP5)-deficient Rats Have Reduced Bone Mass and Abnormal Development of the Retinal Vasculature

Low-density Lipoprotein Receptor-related Protein 5 (LRP5)-deficient Rats Have Reduced Bone Mass and Abnormal Development of the Retinal Vasculature

Genome editing methods in animal models

Genetically Engineering the Nervous System with CRISPR-Cas

Contact Info

Product

Resources

About