FinGMice, the national technology platform for the generation, analysis, and archiving of rodent models for biomedical research, is a consortium composed of six nodes that jointly provide services in Finland. The nodes provide services in generating genetically modified (GM) mouse and rat models for both national and international research communities. Furthermore, phenotyping services requiring high-level expertise are provided by several FinGMice nodes. Those range from semi-automatic processing of tissues to specialist consultations on various organ systems and behavioral tests.

GM mice remain important model organisms for understanding the molecular basis of health and disease in man and serve as suitable animal models for human disease. They, thus, have an important role in the development of new therapeutic approaches to human diseases. Working with GM mice requires specific ethical and legislative issues according to the 3Rs principles, and thus, well-trained personnel are of key importance.


Nodes


Node/Host UniversityNode PI
Transgenic and Tissue Phenotyping (TTP) core facility, Biocenter Oulu (BCO), UO
Reetta Hinttala, UO, reetta.hinttala@oulu.fi
GM unit, Laboratory Animal Centre, HiLIFE, UH
Satu Kuure/Pirjo Laakkonen, UH
satu.kuure@helsinki.fi; pirjo.laakkonen@helsinki.fi
Turku Center of Disease Modeling (TCDM), UTU
Petra Sipilä, UTU
petra.sipila@utu.fi
Finnish Centre for Laboratory Animal Pathology (FCLAP), UH
Jere Lindén, UH
jere.linden@helsinki.fi
Mouse behavioral phenotyping facility (MBPF), Neuroscience Center, HiLIFE, UH
Vootele Võikar, UH
vootele.voikar@helsinki.fi
Neurophenotyping core facility, Biocenter Kuopio (BCK), UEF
Heikki Tanila, UEF
heikki.tanila@uef.fi

UEF: University of Eastern Finland; UH: University of Helsinki; UO: University
of Oulu; UTU: University of Turku; TAU: Tampere University



Contact details


Chair
Reetta Hinttala / +358-(0)294 486135 / reetta.hinttala (at) oulu.fi,
Biocenter Oulu, University of Oulu



Services


Biocenter Oulu Transgenic and Tissue Phenotyping Core Facility


GENERATION OF GM MICE
CRISPR/CAS9 design and electroporation, DNA pronuclear injection, ES cell targeting and morula injection.

CRYOPRESERVATION
Mouse lines cryopreserved by sperm freezing or embryo freezing.

REDERIVATION
Recovery of a mouse line either via in vitro fertilization (IVF) with frozen sperm or transfer of frozen embryos.
Rederivation of contaminated mouse lines either via in vitro fertilization (IVF) or transfer of morula stage embryos.

INTERNATIONAL SHIPMENTS
Shipping and receiving cryopreserved GM strains.

GENERATION OF INDUCED PLURIPOTENT STEM (IPS) CELLS
Fibroblasts induced either by episomal reprogramming (human) or retroviral infection (mouse).

ISOLATION OF EMBRYONIC STEM (ES) CELLS
The 2i ES method to isolate and expand the ES cells from the requested mouse line.

HISTOPATHOLOGY SERVICES
Facilities and services for preparation, staining, and scanning of histology samples. Hamamatsu S60 is used for brightfield scanning of tissue slides. Visiopharm software and APP design is provided as a service for the machine learning-based image analysis of tissue properties.

GM unit of the Laboratory Animal Center at University of Helsinki


DESIGN & GENERATION OF GM-RODENTS
DNA pronuclear injection (mouse) and CRISPR/CAS9 (mouse and rat).
Embryonic stem cell culture
Morula aggregation

CRYOPRESERVATION
Embryo (mouse and rat) and sperm freezing (mouse).

REDERIVATION
Strain recovery from frozen embryos (mouse and rat) and sperm (mouse).
Pathogen removal (mouse and rat)

INTERNATIONAL SHIPMENTS
Shipping and receiving cryopreserved GM strains.

TCDM


DESIGN AND GENERATION OF GM MOUSE MODELS
Pronucleus injection, ES targeting, CRISPR-Cas9 mutations

GENERATION OF XENOGRAFT MOUSE MODELS
Xenografts and syngenic models, drug treatments

MOUSE LINE CRYOPRESERVATION
Embryos, sperm

REDERIVATION
Mouse strain recovery from frozen embryos or sperm
Pathogen removal

INTERNATIONAL SHIPMENTS
Shipping and receiving cryopreserved GM strains

PHARMACOLOGICAL, DIETARY AND SURGICAL INTERVENTIONS
MOUSE COLONY MANAGEMENT

CELL CULTURE
Mouse ES cells, human cancer cell lines, patient-derived cells

HISTOPATHOLOGY SERVICE
From tissue processing to image quantitation (in collaboration with Inst. of Biomedicine Histocore)

PHENOTYPING (COLLABORATION BASED)
  • Animal imaging: PET/CT, magnetic resonance, ultrasound and optical imaging
  • Bone biology: X-ray analyses, bone histomorphometry, mineral content, tension strength
  • Cardiovascular research: In vitro assessment of cardiac and vascular functions by isometric micromyography, Langendorf perfused heart preparation and Radnoti working heart model
  • Clinical chemistry: Sensitive immunoflurometric assayas (Delfia), Elisa kits, Multiplex immunoassays
  • Intestinal diseases: Colitis (colonic inflammation, inflammatory bowel diseases) and colon cancer analyses
  • Neuroendocrinology: Quantitative and in situ expression analyses of neuropeptides and receptors at the gene and protein levels in specific brain regions, analysis of hormonal and gene/protein expression in hypothalamus and pituitary
  • Nutrition and Metabolism: Various dietary interventions, food intake and feeding behavior, energy expenditure, physical activity, body composition, adipose tissue morphology and function, body temperature, glucose and lipid metabolism, hepatosteatosis
  • Reproduction: analyses of reproductive performance, in vitro fertilization (IVF), sperm morphological, functional (capacitation, acrosome reaction) and motility (CASA) analyses
  • Tumor Biology: Generation of xenograft models, genetically modified mouse tumor models and chemically induced cancer models, tumor growth follow-up (palpations, optical imaging), treatment trials
  • Urodynamics: Bladder pressure recordings, urine flow rates, measurements of electrical activities of the urethral striated muscle

Finnish Centre for Laboratory Animal Pathology


HISTOTECHNOLOGY
Trimming, processing and paraffin embedding of tissue specimens for histology
Preparation of unstained and stained sections (HE and a range of special stains)
Immunohistochemistry (markers used in diagnostic veterinary pathology)
Preparation of frozen sections, subsequent staining and IH
Consultation and tutoring on histological tissue processing

PATHOLOGY
Assessment of morphological changes from a wide range of experiments and in the development of new experimental protocols
Necropsy and tissue/sample collection
Assistance with experimental design and morphological techniques

RESEARCH COOPERATION
Involvement of pathologists in interdisciplinary research; experimental approach and protocols, histological assessment, interpretation, further studies etc.

Mouse Behavioral Phenotyping Facility (MBPF)


FULL SERVICE
All testing performed and analyzed by MBPF staff. At the end of the study, MBPF will provide all raw data, analyzed results, and necessary documents as a final project report and present the result at a final project meeting if desired.

TRAINING SERVICE
All testing performed by staff from your group after training by MBPF staff. Analysis of the data can be performed either by your or MBPF staff. At the end of the study, MBPF will provide all raw data and necessary documents.

MINIMUM SERVICE
All testing performed and analyzed by staff from your own group after introduction. At the end of the study, MBPF will provide all raw data and necessary documents as a raw project report.

LIST OF AVAILABLE TESTS

  • Circadian activity – single housed animals (InfraMot), group-housed animals (IntelliCage)
  • Automated home-cage – behavior and cognitive performance in automated, social home cage without experimenter interference (IntelliCage)
  • Emotional behavior – elevated plus-maze, elevated zero-maze, novelty-suppressed feeding, object exploration, open field, light-dark box, forced swim test, tail suspension test, anhedonia (saccharin preference), stress-induced hyperthermia
  • Learning & memory – water maze, Barnes maze, radial maze, T-maze, Y-maze, classical fear conditioning (+extinction), novel object recognition, conditioned taste aversion
  • Motor behavior – accelerating rotarod, grip strength, beam walking, multiple rods, wire hanging, cylinder test, vertical grid
  • Hearing, sensorimotor gating – acoustic startle response, pre-pulse inhibition (PPI) of acoustic startle
  • Nociception – hot plate, plantar test, von Frey test
  • Olfaction – olfactory habituation/dishabituation
  • Vision – visual cliff
  • Social behavior – dyadic social interaction, sociability in 3-compartment test, social preference/avoidance, dominance (tube test), ultrasonic vocalizations
  • Species-specific behavior – nest building, burrowing, grooming, marble burying
  • Stress models – restraint stress, social defeat

Phenotyping Center, Biocenter Kuopio


A. BEHAVIORAL TESTING

  • A1 Motor tests
    Automated monitoring of spontaneous activity, Rotarod, Beam walking, Catwalk, Grid hanging, Cylinder test, Hurdle test, Turning preference, Sensorimotor reflexes
  • A2 Sensory tests
    Pain (hotplate, tail flick), Tactile sensitivity (von Frey Hairs), Hearing (acoustic startle + prepulse inhibition), Vision (edge test, visual discrimination), Olfaction (olfactory threshold, discrimination),
  • A3 Emotion tests
    Elevated plusmaze, Light-dark box, Open field, Marble burying, CO2 panic test, Forced swimming test, Tail suspension test, Sucrose preference, Fear conditioning
  • A4 Tests for addiction
    Ethanol preference, Ethanol tolerance, Conditioned place preference, Conditioned taste preference
  • A5 Social behavior
    Social interaction, Sociability, Territorial aggression
  • A6 Cognitive tests
    Short-term memory (spontaneous alternation in the Y-maze and T-mazes; rewarded delayed alternation in T-maze; working memory test in 8-arm radial maze, novel object recognition)
    Long-term memory (Morris swim task ‘water maze’; position preference in the T-maze; long-term memory version of the 8-arm radial maze; fear conditioning; novel object recognition; odor discrimination)
    Cognitive flexibility (position reversal in the T-maze; new platform position in Morris swim task)
    Planning (nest building)

B. ELECTROPHYSIOLOGY

  • B1 Video-EEG in freely moving mice/rats
    Cortical 24/7 up to two weeks, Multichannel (up to 16 including EMG) up to 6 h
  • B2 Evoked potentials in awake mice/rats
    Visual (flash, pattern), Auditory (click, natural sounds), Somatosensory (electric stim in anesthesia, air puff in awake)
  • B3 In vivo LTP/LTD (anesthesia and awake)

C. INDUCED MODELS
C1 Stereotactic brain microinjections for delivery of: Viral vectors, Drugs or Neurotoxins for targeted lesion

D. METABOLIC TESTS

  • D1 O2, CO2, activity, food/water intake monitoring
  • D2 Assessment of glucose metabolism
    Glucose tolerance test and Insulin tolerance test

E. IN VIVO BRAIN IMAGING (IN COLLABORATION WITH BIOLOGICAL IMAGING CORE FACILITY AT BCK)
Structural MRI (incl. DTI tractography), Functional MRI, Micro-PET

F. CARDIAC ULTRASOUND
Vevo 2100 high-frequency and high-resolution ultrasound system
Basics of Echocardiography and Doppler measurements well covered
Ultrasound imaging of vascular diseases also possible (e.g. abdominal aortic aneurysm)
Targeted delivery of e.g. gene therapy to the heart muscle under guidance of ultrasound visualization

G. HISTOPATHOLOGY
Special immohistochemical stainings, Conventional and fluorescence microscopy, Confocal microscopy (in collaboration with Cellular Imaging Core Facility at BCK), Histological slide scanning (in collaboration with Biobank at Kuopio University Hospital), Quantitative image analysis


Recent user publications


Gabriela Guedes, Shiqi Wang, Flavia Fontana, Patrícia Figueiredo, Jere Lindén, Alexandra Correia, Ricardo J. B. Pinto, Sami Hietala, Filipa L. Sousa, Hélder A. Santos. Dual-Crosslinked Dynamic Hydrogel Incorporating Mo154 with pH and NIR Responsiveness for Chemo-Photothermal Therapy. Advanced Materials. 2021;33(40):2007761. doi:10.1002/adma.202007761

Pavic K, Gupta N, Omella JD, Derua R, Aakula A, Huhtaniemi R, Määttä JA, Höfflin N, Okkeri J, Wang Z, Kauko O, Varjus R, Honkanen H, Abankwa D, Köhn M, Hytönen VP, Xu W, Nilsson J, Page R, Janssens V, Leitner A, Westermarck J. Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A.Nat Commun . 2023 Feb 28;14(1):1143. doi: 10.1038/s41467-023-36693-9.

Devarajan R, Izzi V, Peltoketo H, Rask G, Kauppila S, Väisänen MR, Ruotsalainen H, Martínez-Nieto G, Karppinen SM, Väisänen T, Kaur I, Koivunen J, Sasaki T, Winqvist R, Manninen A, Wärnberg F, Sund M, Pihlajaniemi T, Heljasvaara R. Targeting collagen XVIII improves the efficiency of ErbB inhibitors in breast cancer models. J Clin Invest. 2023 Sep 15;133(18):e159181. doi: 10.1172/JCI159181.

Rafael Moliner, Mykhailo Girych, Cecilia A. Brunello, Vera Kovaleva, Caroline Biojone, Giray Enkavi, Lina Antenucci, Erik F. Kot, Sergey A. Goncharuk, Katja Kaurinkoski, Mirjami Kuutti, Senem M. Fred, Lauri V. Elsilä, Sven Sakson, Cecilia Cannarozzo, Cassiano R. A. F. Diniz, Nina Seiffert, Anna Rubiolo, Hele Haapaniemi, Elsa Meshi, Elina Nagaeva, Tiina Öhman, Tomasz Róg, Esko Kankuri, Marçal Vilar, Markku Varjosalo, Esa R. Korpi, Perttu Permi, Konstantin S. Mineev, Mart Saarma, Ilpo Vattulainen, Plinio C. Casarotto, Eero Castrén Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nat Neurosci 26, 1032–1041 (2023). https://doi.org/10.1038/s41593-023-01316-5

Antila, S., Chilov, D., Nurmi, H. et al. Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer’s disease-related amyloid pathology. Nat Cardiovasc Res 3, 474–491 (2024). https://doi.org/10.1038/s44161-024-00445-9


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These photos are from the material bank of University of Oulu and they are taken by photographer Mikko Törmänen

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