Point Mutation Knockin Rat Models

 



Get supplemental information, a quote, and estimated timeframe for generating your point mutation rat line.

 

A point mutation Knockin rat defines an animal model in which one or more nucleotides are constitutively mutated.

Gain or loss of function: The insertion, deletion, nonsense and sense mutations can alter the amino acid sequence of a given protein, and so dramatically affect its function.


Infographic: Point mutation Knockin rat model

Typical applications for point mutation Knockin rat models


For academic research:
  • Study protein function (gain or loss of function)
  • Analyze the role of non-coding regions and regulatory elements
  • Investigate disease-causing mutations
For bio-pharmaceutical research & development:
  • Study drug resistant mutants
  • Alter drug-antibody affinities
  • Pharmacological off-target and efficacy studies
  • Mimic human genetic diseases

Strengths and limitations of point mutation Knockin rat models

+
  • Best way to reproduce human disease when due to mutations
  • High physiological relevancy of the scientific data obtained from the model (regulatory elements conserved, under control of endogenous promoter, expression of all splice variants, etc.) = cleaner way than classical KO where the whole gene is deleted
  • Phenotype due only to the mutation: alteration of a single function without disturbing other domains of a protein
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  • Mutation of the gene of interest may affect development, resulting in an impaired phenotype or embryonic death
    →  Limitation can be bypassed by applying conditions such as time-specific gene inactivation
  • 1. Modification or disruption of splicing regulation
    2. Genetic redundancy
    →  Can be assessed via constitutive Knockout of the gene of interest


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, 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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