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Point mutation KI rats
Rat model generation

Point mutation KI rats

Use a point mutation rat Knockin to circumvent complex phenotypes arising from complete Knockouts (e.g., signaling pathway problems, cross-reactivity).

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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.

Applications

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 of point mutation Knockin mouse 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

Limitations of point mutation Knockin mouse models

  • 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

Validation

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

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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

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

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

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

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Naunyn Schmiedebergs Arch Pharmacol

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

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

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Body distribution of infused serotonin in rats.

Clin Exp Pharmacol Physiol

Jan 2009
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