Quick Knockin Mouse Models (Neutral Locus Targeting: Rosa26, Hprt)


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A Quick Knockin™ mouse defines an animal model in which a transgene is inserted in a permissive locus, also known as neutral locus or safe harbor, such as example Rosa26 and Hprt. The transgene can be constitutively or inducibly overexpressed.

Targeting those loci enable a full control of the copy number and avoid transgene silencing or deregulation of neighboring genes.

Quick Knockin™ Models
  • Fast development
  • Broad range of appplications
1) Technology
  • Versatile (time-/tissue-specific; co-expressions)
  • Robust
2) Design
  • Obtain reliable scientific data
  • Anticipate current and future needs



Learn more and watch the video.

Typical applications for Quick Knockin mouse models

For academic research:
  • Gene function studies by overexpression if Knockout has no or little phenotype
  • Rescue experiment to validate specificity of the Knockout phenotype
  • Protein structure and function studies
  • Expression pattern analysis
  • Expression of specific isoform to decipher its particular function
  • Express human gene that has no mouse orthologue
  • Model of dominant negative or gain-of-function mutation of human disease
For bio-pharmaceutical research & development:
  • Validate drug candidate by expression of mutant form of receptor mimicking its role
  • Validate mutation in target as disease-causing agent
  • Test protective effect on controlled gene expression on disease onset or progression
  • Identification biomarkers in human disease model
  • Get mouse model that cross-reacts with human-specific therapeutic antibody (or similar)

Strengths and limitations of Quick Knockin mouse models

  • Very robust approach due to the wide usage of both, Rosa26 and Hprt, by scientific community
  • Fast development due to ready-to-use vectors
  • Several genetic backgrounds are available (C57Bl/6, BALB/c…)
  • Variety of genetic designs to fit a broad range of applications
  • No physiological regulation of the transgene expression
    →  Limitation can be bypassed by using conventional Knockin approach
  • In most cases only one isoform can be expressed
  • Mutated mouse gene is expressed in presence of the wildtype gene

Case studies and publications on our Quick Knockin™ mouse models

Case studies

Model recapitulating key features of human tauopathies.

Bondulich MK, et al. Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate. Brain. 2016.

Tauopathies are characterized by progressive cognitive and/or motor dysfunction, together with highly phosphorylated aggregates of the microtubule-associated protein tau in brain and peripheral nerve.

Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease.

Model: New highly disease-relevant mouse model of tauopathy expressing Hprt locus-targeted Tau35, highly phosphorylated C-terminal human tau fragment.

Aim: Evaluate a new model of tauopathy for developing novel treatments for human tauopathies.

Results: Tau35 mice represent a pathophysiologically relevant mouse model in which to test new, potentially disease-modifying therapies.


Figure 1. Tau expression in Tau35 mouse brains

Excessive accumulation of cGMP and subsequent rod photoreceptor death, followed by a mutation-independent, secondary death of cone photoreceptors.

Figure 1a - Tau35 mice

A) RT-PCR confirms Tau35 expression.

B) Sagittal sections show widespread hemagglutinin labeling in Tau35 mouse brain (upper panels, scale bar = 2 mm). Higher magnifications of the hippocampal CA1 region show strongly hemagglutinin-positive pyramidal neurons in Tau35 mice (lower panels, scale bar = 200 mm). Western blots of frontal region and hippocampus/associated cortex (HC) show hemagglutinin protein expression only in Tau35 mice.

Figure 1b - Tau35 mice


Figure 2. Progressive neuromuscular impairment

Figure 2a-d - Tau35 mice

A) Limb clasping is apparent in Tau35 mice from 2 months of age (image shows 8 months), with all Tau35 animals affected by 18 months. Clasping is not observed in wildtype (wt) mice at any age examined.

B) Spine curvature is apparent in Tau35, but not wildtype mice, at 14 months of age. A progressive reduction in the kyphotic index in Tau35 mice after 4 months of age indicates increasing spine curvature.

C) Visible platform (VP) training in the Morris water maze was followed by 4 days of hidden platform training. At 10 months of age, Tau35 mice exhibit longer escape latency on the fourth day of testing compared to wildtype mice.

D) The grip strength of Tau35 mice declines steadily with age.


Figure 3. Phenylbutyrate rescues disease-related changes in Tau35 mice.

Figure 3ab - Tau35 mice

A) Morris water maze (10 months) testing of 4-phenylbutyrate (PBA, dotted lines) and vehicle-treated (solid lines) Tau35 (circles) and wildtype (wt, squares) mice. PBA-treated Tau35 mice show improved learning after 3 days, resulting in decreased escape latency.

B) Grip strength of Tau35 (10 months) is restored by PBA treatment.



Eresch J, Stumpf M, Koch A, Vutukuri R, Ferreirós N, Schreiber Y, Schröder K, Devraj K, Popp R, Hattenbach LO, Pfeilschifter J, Pfeilschifter W.
Sphingosine Kinase 2 Modulates Retinal Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy.
Invest Ophthalmol Vis Sci. 2018 Feb 1.

Joshi SS, Tandukar B, Castaneda M, Jiang S, Diwakar G, Hertzano RP, Hornyak TJ.
Characterization of a new, inducible transgenic mouse model with GFP expression in melanocytes and their precursors.
Gene Expr Patterns. 2017 Oct 21.

Schwalm S, Beyer S, Frey H, Haceni R, Grammatikos G, Thomas D, Geisslinger G, Schaefer L, Huwiler A, Pfeilschifter J.
Sphingosine Kinase-2 Deficiency Ameliorates Kidney Fibrosis by Up-Regulating Smad7 in a Mouse Model of Unilateral Ureteral Obstruction.
Am J Pathol. 2017 Aug 12.

Viswambharan H, Yuldasheva NY, Sengupta A, Imrie H, Gage MC, Haywood NJ, Walker AM, Skromna A, Makova N, Galloway SL, Shah P, Sukumar P, Porter KE, Grant PJ, Shah AM, Santos CX, Li J, Beech DJ, Wheatcroft S, Cubbon RM, Kearney MT.
Selective Enhancement of Insulin Sensitivity in the Endothelium In Vivo Reveals a Novel Proatherosclerotic Signalling Loop.
Circ Res. 2016 Dec 5.

Bondulich MK, Guo T, Meehan C, Manion J, Rodriguez Martin T, Mitchell JC, Hortobagyi T, Yankova N, Stygelbout V, Brion JP, Noble W, Hanger DP.
Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate.
Brain. 2016 Jun 12.

Wang J, Zhang X, Wang P, Wang X, Farris AB 3rd, Wang Y.
Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments.
Life Sci Space Res (Amst). 2016 Jun.

Sheen CR, Kuss P, Narisawa S, Yadav MC, Nigro J, Wang W, Chhea TN, Sergienko EA, Kapoor K, Jackson MR, Hoylaerts MF, Pinkerton AB, O'Neill WC, Millán JL.
Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification.
J Bone Miner Res. 2015 May.

López-Soldado I, Zafra D, Duran J, Adrover A, Calbó J, Guinovart JJ.
Liver glycogen reduces food intake and attenuates obesity in a high-fat diet-fed mouse model.
Diabetes. 2015 Mar.

Iqbal AJ, McNeill E, Kapellos TS, Regan-Komito D, Norman S, Burd S, Smart N, Machemer DE, Stylianou E, McShane H, Channon KM, Chawla A, Greaves DR
Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo.
Blood. 2014 Oct 9.

Plucińska K, Crouch B, Koss D, Robinson L, Siebrecht M, Riedel G, Platt B
Knock-in of human BACE1 cleaves murine APP and reiterates Alzheimer-like phenotypes.
J Neurosci. 2014 Aug 6.

McNeill E, Iqbal AJ, Patel J, White GE, Regan-Komito D, Greaves DR, Channon KM
Contrasting in vitro vs. in vivo effects of a cell membrane-specific CC-chemokine binding protein on macrophage chemotaxis.
J Mol Med (Berl). 2014 Aug 1.

Rosendahl A, Niemann G, Lange S, Ahadzadeh E, Krebs C, Contrepas A, van Goor H, Wiech T, Bader M, Schwake M, Peters J, Stahl R, Nguyen G, Wenzel UO
Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice.
Lab Invest. 2014 Aug.

LeBlanc AC, Ramcharitar J, Afonso V, Hamel E, Bennett DA, Pakavathkumar P, Albrecht S
Caspase-6 activity in the CA1 region of the hippocampus induces age-dependent memory impairment.
Cell Death Differ. 2014 May 21.

Clarke SE, Kang JX, Ma DW
The iFat1 transgene permits conditional endogenous n-3 PUFA enrichment both in vitro and in vivo.
Transgenic Res. 2014 Mar 13.

Imudia AN, Wang N, Tanaka Y, White YA, Woods DC, Tilly JL.
Comparative gene expression profiling of adult mouse ovary-derived oogonial stem cells supports a distinct cellular identity.
Fertil Steril. 2013 Nov.

Winkelmann A, Maggio N, Eller J, Caliskan G, Semtner M, Häussler U, Jüttner R, Dugladze T, Smolinsky B, Kowalczyk S, Chronowska E, Schwarz G, Rathjen FG, Rechavi G, Haas CA, Kulik A, Gloveli T, Heinemann U, Meier JC.
Changes in neural network homeostasis trigger neuropsychiatric symptoms.
J Clin Invest. 2014 Jan 16.

Dart DA, Waxman J, Aboagye EO, Bevan CL.
Visualising androgen receptor activity in male and female mice.
PLoS One. 2013 Aug 7.

Gulbins E, Palmada M, Reichel M, Lüth A, Böhmer C, Amato D, Müller CP, Tischbirek CH, Groemer TW, Tabatabai G, Becker KA, Tripal P, Staedtler S, Ackermann TF, van Brederode J, Alzheimer C, Weller M, Lang UE, Kleuser B, Grassmé H, Kornhuber J.
Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs.
Nat Med. 2013 Jul.

Mühle C, Huttner HB, Walter S, Reichel M, Canneva F, Lewczuk P, Gulbins E, Kornhuber J.
Characterization of Acid sphingomyelinase activity in human cerebrospinal fluid.
PLoS One. 2013 May 2.

Ehrmann I, Dalgliesh C, Liu Y, Danilenko M, Crosier M, Overman L, Arthur HM, Lindsay S, Clowry GJ, Venables JP, Fort P, Elliott DJ.
The Tissue-Specific RNA Binding Protein T-STAR Controls Regional Splicing Patterns of Neurexin Pre-mRNAs in the Brain.
PLoS Genet. 2013 Apr.

Ryan D, Koss D, Porcu E, Woodcock H, Robinson L, Platt B, Riedel G.
Spatial learning impairments in PLB1Triple knock-in Alzheimer mice are task-specific and age-dependent.
Cell Mol Life Sci. 2013 Mar 28.

Imrie H, Viswambharan H, Sukumar P, Abbas A, Cubbon RM, Yuldasheva N, Gage M, Smith J, Galloway S, Skromna A, Rashid ST, Futers TS, Xuan S, Gatenby VK, Grant PJ, Channon KM, Beech DJ, Wheatcroft SB, Kearney MT.
Novel role of the IGF-1 receptor in endothelial function and repair: studies in endothelium-targeted IGF-1 receptor transgenic mice.
Diabetes. 2012 Sep.

Duran J, Tevy MF, Garcia-Rocha M, Calbó J, Milán M, Guinovart JJ.
Deleterious effects of neuronal accumulation of glycogen in flies and mice.
EMBO Mol Med. 2012 Aug.

Platt B, Drever B, Koss D, Stoppelkamp S, Jyoti A, Plano A, Utan A, Merrick G, Ryan D, Melis V, Wan H, Mingarelli M, Porcu E, Scrocchi L, Welch A, Riedel G.
Abnormal Cognition, Sleep, EEG and Brain Metabolism in a Novel Knock-In Alzheimer Mouse, PLB1.
PLoS One. 2011 Nov 11.

Needham LA, Davidson AH, Bawden LJ, Belfield A, Bone EA, Brotherton DH, Bryant S, Charlton MH, Clark VL, Davies SJ, Donald A, Day FA, Krige D, Legris V, McDermott J, McGovern Y, Owen J, Patel SR, Pintat S, Testar RJ, Wells GM, Moffat D, Drummond AH.
Drug targeting to monocytes and macrophages using esterase-sensitive chemical motifs.
J Pharmacol Exp Ther. 2011 Oct.

van den Born E, Vågbø CB, Songe-Møller L, Leihne V, Lien GF, Leszczynska G, Malkiewicz A, Krokan HE, Kirpekar F, Klungland A, Falnes PØ.
ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA.
Nat Commun. 2011 Feb 1.


Jones T, Jones PL.
A cre-inducible DUX4 transgenic mouse model for investigating facioscapulohumeral muscular dystrophy.
PLoS One. 2018 Feb 7.

van de Beek MC, Dijkstra IM, van Lenthe H, Ofman R, Goldhaber-Pasillas D, Schauer N, Schackmann M, Engelen-Lee JY, Vaz FM, Kulik W, Wanders RJ, Engelen M, Kemp S.
C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man.
PLoS One. 2016 Apr 28.

Sportoletti P, Varasano E, Rossi R, Bereshchenko O, Cecchini D, Gionfriddo I, Bolli N, Tiacci E, Intermesoli T, Zanghì P, Masciulli A, Martelli MP, Falzetti F, Martelli MF, Falini B.
The human NPM1 mutation A perturbs megakaryopoiesis in a conditional mouse model.
Blood. 2013 Apr 25.

van den Born E, Vågbø CB, Songe-Møller L, Leihne V, Lien GF, Leszczynska G, Malkiewicz A, Krokan HE, Kirpekar F, Klungland A, Falnes PØ.
ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA.
Nat Commun. 2011 Feb 1.

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