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Tissue-specific KO rats
Rat model generation

Tissue-specific KO rats

Use  tissue- or cell-specific conditional Knockout rat models to bypass embryonic lethality,  compensatory mechanisms, complex phenotypes, etc.

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A tissue-specific Knockout rat defines an animal model in which a gene of interest is "floxed" and thus inactivatable in specific cell types in a certain tissue (conditional). Other cell types and tissues exhibit an unmodified, functional gene expression.

This gene inactivation is achieved by an additional breeding step with a tissue- or cell type-specific Cre-deleter rat line. The creation process of such models also gives access to whole body (constitutive) Knockouts

Applications

For academic research:

  • Study gene function in one specific organ, tissue or cell type
  • Mimic pathologies caused by gene inactivation in a given cell type
  • Create a tissue-specific phenotype for multi-function proteins

For bio-pharmaceutical research & development:

  • Validate target genes with cell-specific functions
  • Investigate signaling pathways in certain cell types
  • Safety studies

Strengths of tissue-specific Knockout rat models

  • Very flexible: easy switch to study another tissue
  • High physiological relevancy of the obtained scientific data from such a model
  • Enables access as well to constitutive Knockout for comparison studies

Limitations of tissue-specific Knockout rat models

  • Rat line creation requires the insertion of exogenous sequences (loxP, FRT) that can deregulate transcription and splicing
    → Risk can be greatly minimized by applying in-depth bio-informatic, genetic, and bibliographic analysis
  • Few deleter rats are available, requiring the creation of new Cre-deleter rats
    → New tissue- or cell-specific Cre rat lines can be produced by genOway in parallel to the conditional rat model
  • Inactivation of the gene of interest in one cell type may occur during cell type differentiation, resulting in an impaired phenotype and/or modified cell physiology
    →  Limitation can be bypassed by applying conditions such as time-specific gene inactivation
  • To obtain tissue specificity, a crossing step with a deleter rat line implies a time-consuming production of cohorts
    →  This "time" issue must be anticipated and integrated in the scientific consulting prior to model development

Validation

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Efficient generation of human immune system rats using human CD34+ cells

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Brain-derived Estrogen: A Critical Player in Maintaining Cognitive Health of Aged Female Rats, Possibly Involving GPR30

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Early lysosome defects precede neurodegeneration with amyloid-β and tau aggregation in NHE6-null rat brain

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The Lrat-/- Rat: CRISPR/Cas9 Construction and Phenotyping of a New Animal Model for Retinitis Pigmentosa

Int J Mol Sci

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Long Acellular Nerve Allografts Cap Transected Nerve to Arrest Axon Regeneration and Alter Upstream Gene Expression in a Rat Neuroma Model

Plast Reconstr Surg

May 2021
Comparison of Myelin-Associated Glycoprotein With Vincristine for Facial Nerve Inhibition After Bilateral Axotomy in a Transgenic Thy1-Gfp Rat Model

JAMA Facial Plast Surg

May 2019
Assessment of fear and anxiety associated behaviors, physiology and neural circuits in rats with reduced serotonin transporter (SERT) levels

Transl Psychiatry

Jan 2019
Constitutive serotonin transporter reduction resembles maternal separation with regard to stress-related gene expression

ACS Chem Neurosci

Nov 2018
5-HT3 receptor signaling in serotonin transporter knockout rats: a female sex specific animal model of visceral hypersensitivity.

Am J Physiol Gastrointest Liver Physiol

Oct 2018
Generation of immunodeficient rats with Rag1 and Il2rg gene deletions and human tissue grafting models.

Transplantation

Apr 2018
Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats.

Eur J Pharmacol

Jan 2015
Serotonin Reuptake Transporter Deficiency Modulates the Acute Thermoregulatory and Locomotor Activity Response to 3,4-({+/-})-Methylenedioxymethamphetamine, and Attenuates Depletions in Serotonin Levels in SERT-KO Rats

Toxicol Sci

Mar 2014
Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence.

Exp Neurol

Sep 2013
Nitric oxide regulates cardiac intracellular Na+ and Ca2+ by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism.

J Mol Cell Cardiol

Aug 2013
Visceral hypersensitivity in female but not in male serotonin transporter knockout rats.

Neurogastroenterol Motil

Jun 2013
Generation of Rag1-knockout immunodeficient rats and mice using engineered meganucleases.

FASEB J

Feb 2013
Mesenchymal stem cell therapy prevents IFTA in a rat kidney allograft model

Stem Cells Dev

Nov 2012
Geldanamycin accelerated peripheral nerve regeneration in comparison to FK-506 in vivo.

Neuroscience

Oct 2012
A transgenic rat expressing green fluorescent protein (GFP) in peripheral nerves provides a new hindlimb model for the study of nerve injury and regeneration

J Neurosci Methods

Feb 2012
Effects of Human Alpha-Synuclein A53T-A30P Mutations on SVZ and Local Olfactory Bulb Cell Proliferation in a Transgenic Rat Model of Parkinson Disease

Parkinsons Dis

Jun 2011
Comparison of the function of the serotonin transporter in the vasculature of male and female rats

Clin Exp Pharmacol Physiol

May 2011
Lack of the serotonin transporter (SERT) reduces the ability of 5-hydroxytryptamine to lower blood pressure.

Naunyn Schmiedebergs Arch Pharmacol

May 2011
Pharmacological blockade or genetic knockout of the NOP receptor potentiates the rewarding effect of morphine in rats.

Drug Alcohol Depend

Apr 2011
Serotonin transporter interacts with the PDGFβ receptor in PDGF-BB-induced signaling and mitogenesis in pulmonary artery smooth muscle cells

Am J Physiol Lung Cell Mol Physiol

Mar 2011
Nociceptin/orphanin FQ receptor knockout rats: in vitro and in vivo studies.

Neuropharmacology

Mar 2011
A New Model for Facial Nerve Research: the novel transgenic Thy1-GFP rat

Arch Facial Plast Surg

Sep 2010
Identification of genetic modifiers of behavorial phenotypes in serotonin transporter knockout rats

BMC Genetics

May 2010
Body distribution of infused serotonin in rats.

Clin Exp Pharmacol Physiol

May 2009
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