Tissue-Specific Conditional Knockout Rat Models

 



Get supplemental information, a quote, and estimated timeframe to generate your tissue-specific KO rat line.

 

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. 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.


Infographic: Tissue-specific Knockout rat model

Typical applications for tissue-specific Knockout rat models


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 and limitations of tissue-specific Knockout rat models

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  • 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
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  • 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


Selection of genOway clients' publications on rat models

Pain

Micheli L, Di Cesare Mannelli L, Guerrini R, Trapella C, Zanardelli M, Ciccocioppo R, Rizzi A, Ghelardini C, Calò G.
Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats.
Eur J Pharmacol. 2015

Galligan JJ, Patel BA, Schneider SP, Wang H, Zhao H, Novotny M, Bian X, Kabeer R, Fried D, Swain GM.
Visceral hypersensitivity in female but not in male serotonin transporter knockout rats.
Neurogastroenterol Motil. 2013

Thermoregulation

Lizarraga LE, Phan AV, Cholanians AB, Herndon JM, Lau SS, Monks TJ
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. 2014

Neuronal regeneration

Saheb-Al-Zamani M, Yan Y, Farber SJ, Hunter DA, Newton P, Wood MD, Stewart SA, Johnson PJ, Mackinnon SE.
Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence.
Exp Neurol. 2013

Sun HH, Saheb-Al-Zamani M, Yan Y, Hunter DA, Mackinnon SE, Johnson PJ.
Geldanamycin accelerated peripheral nerve regeneration in comparison to FK-506 in vivo.
Neuroscience. 2012

Moore AM, Borschel GH, Santosa KA, Flagg ER, Tong AY, Kasukurthi R, Newton P, Yan Y, Hunter DA, Johnson PJ, Mackinnon SE.
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. 2012

Magill CK, Moore AM, Borschel GH, Mackinnon SE.
A new model for facial nerve research: the novel transgenic Thy1-GFP rat.
Arch Facial Plast Surg. 2010

Immunodeficiency

Ménoret S, Ouisse LH, Tesson L, Delbos F, Garnier D, Remy S, Usal C, Concordet JP, Giovannangeli C, Chenouard V, Brusselle L, Merieau E, Nerrière-Daguin V, Duteille F, Bellier-Waast F, Fraichard A, Nguyen TH, Anegon I.
Generation of immunodeficient rats with Rag1 and Il2rg gene deletions and human tissue grafting models.
Transplantation. 2018

Ménoret S, Fontanière S, Jantz D, Tesson L, Thinard R, Rémy S, Usal C, Ouisse LH, Fraichard A, Anegon I.
Generation of Rag1-knockout immunodeficient rats and mice using engineered meganucleases.
FASEB J. 2013

Cardiac function

Pavlovic D, Hall AR, Kennington EJ, Aughton K, Boguslavskyii A, Fuller W, Despa S, Bers DM, Shattock MJ.
Nitric oxide regulates cardiac intracellular Na+ and Ca2+ by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism.
J Mol Cell Cardiol. 2013

Transplantation

Franquesa M, Herrero E, Torras J, Ripoll E, Flaquer M, Gomà M, Lloberas N, Anegon I, Cruzado JM, Grinyó JM, Herrero-Fresneda I.
Mesenchymal Stem Cell Therapy Prevents Interstitial Fibrosis and Tubular Atrophy in a Rat Kidney Allograft Model.
Stem Cells Dev. 2012

Parkinson disease

Lelan F, Boyer C, Thinard R, Rémy S, Usal C, Tesson L, Anegon I, Neveu I, Damier P, Naveilhan P, Lescaudron L.
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. 2011

Hypertension

Patrick Davis R, Linder AE, Watts SW.
Lack of the serotonin transporter (SERT) reduces the ability of 5-hydroxytryptamine to lower blood pressure.
Naunyn Schmiedebergs Arch Pharmacol. 2011

Depression

Linder AE, Davis RP, Burnett R, Watts SW.
Comparison of the function of the serotonin transporter in the vasculature of male and female rats.
Clin Exp Pharmacol Physiol. 2011

Respiration

Ren W, Watts SW, Fanburg BL.
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. 2011

Anxiety

Rizzi A, Molinari S, Marti M, Marzola G, Calo' G.
Nociceptin/orphanin FQ receptor knockout rats: in vitro and in vivo studies.
Neuropharmacology. 2011

Drug abuse

Rutten K, De Vry J, Bruckmann W, Tzschentke TM.
Pharmacological blockade or genetic knockout of the NOP receptor potentiates the rewarding effect of morphine in rats.
Drug Alcohol Depend. 2011

Physiology

Linder AE, Beggs KM, Burnett RJ, Watts SW.
Body distribution of infused serotonin in rats.
Clin Exp Pharmacol Physiol. 2009

 

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