The Generative Brain

CISA-INIA, Centro de Investigacion en Sanidad Animal, Valdeolmos, Spain (prion group)

CISA is the Spanish animal health research centre at Valdeolmos, outside Madrid, created in 1993 and now part of the INIA within the CSIC. Its high containment installation is one of the largest in Spain, with 40 laboratories, 19 animal units and space for species from fish to horses. Inside it sits a prion group that has worked since at least 2005 on experimental transmission of prions in transgenic mice. The group's distinctive asset is a collection of mouse lines expressing the prion protein of different species, including the human PrP lines Hu-Tg340 and Hu-Tg372, the bovine line Bo-Tg110 and a macaque line. Because those lines are the standard way to tell human prion strains apart and to measure how much infectivity a tissue or a decontamination step leaves behind, the group turns up as a partner on much of the European human prion work in this atlas: the Toulouse peripheral tissue and bone marrow studies, the EFS decontamination work and the INRAE Jouy-en-Josas inactivation work. Information only, not medical advice.

Key facts

  • The CISA high biosafety laboratory was created in 1993 at Carretera Algete-El Casar de Talamanca km 8.1, 28130 Valdeolmos, Madrid, with the mission of studying, preventing and controlling infectious and exotic diseases of Spanish livestock and wild fauna.
  • The centre depends on the INIA, which in turn depends on the CSIC; containment is Biological Containment Level 3 under the WHO classification and level 4 under the World Organisation for Animal Health classification, with two laboratories cleared for exotic high-risk viruses that can affect humans, described as the highest level in Spain. The installation has 40 laboratories and common rooms, 19 animal units and 10,824 square metres.
  • The INIA was moved into the CSIC by a Royal Decree approved by the Spanish Council of Ministers on 30 March 2021, together with the oceanography and geology institutes, with the three bodies keeping their names and activities; this is why papers from 2021 onward carry the affiliation CISA-INIA-CSIC while older ones read INIA-CISA or CISA/INIA.
  • A Europe PMC affiliation search returns 77 records tying CISA to prion or Creutzfeldt-Jakob work from 2005 to 2026, the earliest being a 2005 Journal of Virology study of vertical transmission of BSE prions in a transgenic mouse model; recurring authors are Espinosa JC, Marin-Moreno A, Torres JM, Aguilar-Calvo P and Fernandez-Borges N.
  • The group's human PrP mouse lines are named in its own papers: Hu-Tg340 expressing wild-type human PrP with methionine at codon 129, the loop mutant line VDQ-HuTg372, and tg650, used alongside the bovine line Bo-Tg110 and a macaque PrP line TgMac.
  • In a 2019 Scientific Reports paper with the CEA at Fontenay-aux-Roses, five of eight authors were at CISA Valdeolmos; macaque PrP and human PrP mice behaved alike for most strains, but the macaque line was more susceptible to classical BSE, which matters for how macaque experiments are read as a proxy for human risk.
  • A CISA author contributed the mouse bioassay side of two human iatrogenic risk studies led from Toulouse: bone marrow from seven of eight sporadic CJD patients carried unexpectedly high infectivity (J Pathol 2017), and infectivity was found in a wide range of peripheral tissues of sporadic and variant CJD patients at levels varying unpredictably between tissues and patients (Acta Neuropathologica 2021).
  • CISA also supplied the bovine PrP tgBov Tg110 bioassay used in the 2020 EFS mSphere study that compared Surf-PMCA with infectivity after decontamination, the study that found several commercial reagents largely ineffective against variant CJD prions despite approval on the hamster 263K model.
  • A CISA author is on the 2020 mBio paper showing that prions from sporadic CJD patients propagate as strain mixtures, where 29 isolates transmitted into human PrP mice resolved into the M1 and V2 strains and a targeted assay found V2 in more than 80 percent of isolates.
  • In a 2025 Journal of Hospital Infection study led from INRAE Jouy-en-Josas with a CISA coauthor, a TFD Premium formulation inactivated human prions better than 1 N sodium hydroxide for one hour at room temperature, and sporadic CJD VV2 prions in Tg650 mice resisted inactivation more than variant CJD prions.
  • A 2026 paper with all five authors at CISA measured what histology processing does to infectivity: formalin fixation only modestly prolonged incubation, while formic acid cut infectivity by about 4.4 log10 for variant CJD and about 5 log10 for sporadic CJD, with residual infectivity still detectable in the mouse bioassay.
  • The group also works on spontaneous disease models: a 2025 PLoS Pathogens paper with SISSA Trieste and the Istituto Neurologico Carlo Besta reported that mice carrying a histidine 95 to tyrosine substitution in PrP fell ill at about 100 days with spongiform change and protease-resistant PrP, and that their brain material transmitted lethal disease to Tga20 mice.
  • No official CISA or INIA-CSIC page naming the prion group was found. The CSIC bioinformatics hub lists three CISA groups, none of them a prion group, and the ministry page describing the installation does not mention prions at all; a public profile page describes one CISA scientist as a senior scientist working on prions and neurodegenerative diseases.

Timeline

  1. 1993CISA high biosafety laboratory created at Valdeolmos.
  2. 2005Earliest prion paper found with a CISA affiliation: vertical transmission of BSE prions in a transgenic mouse model, Journal of Virology.
  3. 2011PLoS Pathogens paper with CISA and INRA Jouy-en-Josas authors shows sheep and goat BSE propagating more efficiently than cattle BSE in the human PrP lines tg650 and tg340.
  4. 2017Journal of Pathology paper with Toulouse, APHA, CISA and Edinburgh reports infectivity in bone marrow from sporadic CJD patients.
  5. 2019Scientific Reports comparison of macaque and human PrP transgenic mice, led from CISA with the CEA.
  6. 2020mSphere decontamination study using the CISA bovine PrP mouse bioassay alongside EFS Surf-PMCA.
  7. 2020mBio paper on sporadic CJD prions propagating as strain mixtures, with a CISA coauthor.
  8. 2020Review of transgenic mouse models for prion disease published by three CISA authors.
  9. 2021Acta Neuropathologica paper on wide distribution of prion infectivity in peripheral tissues of variant and sporadic CJD patients, with a CISA coauthor.
  10. 2021Spanish Council of Ministers approves the Royal Decree integrating the INIA into the CSIC.
  11. 2025Journal of Hospital Infection study of new decontamination procedures against human prions, INRAE Jouy-en-Josas with CISA.
  12. 2025PLoS Pathogens paper on spontaneous neurodegeneration in H95Y PrP transgenic mice, led from CISA with Italian partners.
  13. 2026Journal of General Virology paper from CISA on formic acid and formalin effects on sporadic and variant CJD infectivity in histological samples.
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