Modeling Rare Human Disorders in Mice: The Finnish Disease Heritage

doi:10.3390/cells10113158

Review

. 2021 Nov 13;10(11):3158.

doi: 10.3390/cells10113158.

Modeling Rare Human Disorders in Mice: The Finnish Disease Heritage

Tomáš Zárybnický¹, Anne Heikkinen^{2

3}, Salla M Kangas^{2

4

5}, Marika Karikoski⁶, Guillermo Antonio Martínez-Nieto^{6

7}, Miia H Salo^{2

4

5}, Johanna Uusimaa^{4

5

8}, Reetta Vuolteenaho², Reetta Hinttala^{2

4

5}, Petra Sipilä^{6

7}, Satu Kuure^{1

9}

Affiliations

¹ Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, P.O. Box 63, 00014 Helsinki, Finland.
² Biocenter Oulu, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland.
³ Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 8000, 90014 Oulu, Finland.
⁴ PEDEGO Research Unit, University of Oulu, P.O. Box 8000, 90014 Oulu, Finland.
⁵ Medical Research Center, Oulu University Hospital, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland.
⁶ Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
⁷ Turku Center for Disease Modelling (TCDM), Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
⁸ Clinic for Children and Adolescents, Division of Pediatric Neurology, Oulu University Hospital, P.O. Box 20, 90029 Oulu, Finland.
⁹ GM-Unit, Laboratory Animal Center, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, Finland.

PMID: 34831381
PMCID: PMC8621025
DOI: 10.3390/cells10113158

Review

Modeling Rare Human Disorders in Mice: The Finnish Disease Heritage

Tomáš Zárybnický et al. Cells. 2021.

. 2021 Nov 13;10(11):3158.

doi: 10.3390/cells10113158.

Authors

Affiliations

¹ Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, P.O. Box 63, 00014 Helsinki, Finland.
² Biocenter Oulu, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland.
³ Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 8000, 90014 Oulu, Finland.
⁴ PEDEGO Research Unit, University of Oulu, P.O. Box 8000, 90014 Oulu, Finland.
⁵ Medical Research Center, Oulu University Hospital, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland.
⁶ Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
⁷ Turku Center for Disease Modelling (TCDM), Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
⁸ Clinic for Children and Adolescents, Division of Pediatric Neurology, Oulu University Hospital, P.O. Box 20, 90029 Oulu, Finland.
⁹ GM-Unit, Laboratory Animal Center, Helsinki Institute of Life Science, University of Helsinki, 00790 Helsinki, Finland.

PMID: 34831381
PMCID: PMC8621025
DOI: 10.3390/cells10113158

Abstract

The modification of genes in animal models has evidently and comprehensively improved our knowledge on proteins and signaling pathways in human physiology and pathology. In this review, we discuss almost 40 monogenic rare diseases that are enriched in the Finnish population and defined as the Finnish disease heritage (FDH). We will highlight how gene-modified mouse models have greatly facilitated the understanding of the pathological manifestations of these diseases and how some of the diseases still lack proper models. We urge the establishment of subsequent international consortiums to cooperatively plan and carry out future human disease modeling strategies. Detailed information on disease mechanisms brings along broader understanding of the molecular pathways they act along both parallel and transverse to the proteins affected in rare diseases, therefore also aiding understanding of common disease pathologies.

Keywords: CRISPR/Cas9; Finnish disease heritage; genome engineering; monogenic diseases; mouse models; rare diseases.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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References

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[1] Little M.H., Combes A.N. Kidney organoids: Accurate models or fortunate accidents. Genes Dev. 2019;33:1319–1345. doi: 10.1101/gad.329573.119. - DOI - PMC - PubMed

[2] Little M.H., Combes A.N. Kidney organoids: Accurate models or fortunate accidents. Genes Dev. 2019;33:1319–1345. doi: 10.1101/gad.329573.119. - DOI - PMC - PubMed

[3] Schutgens F., Clevers H. Human Organoids: Tools for Understanding Biology and Treating Diseases. Annu. Rev. Pathol. Mech. Dis. 2020;15:211–234. doi: 10.1146/annurev-pathmechdis-012419-032611. - DOI - PubMed

[4] Schutgens F., Clevers H. Human Organoids: Tools for Understanding Biology and Treating Diseases. Annu. Rev. Pathol. Mech. Dis. 2020;15:211–234. doi: 10.1146/annurev-pathmechdis-012419-032611. - DOI - PubMed

[5] Milne T.A. Mouse models of MLL leukemia: Recapitulating the human disease. Blood. 2017;129:2217–2223. doi: 10.1182/blood-2016-10-691428. - DOI - PMC - PubMed

[6] Milne T.A. Mouse models of MLL leukemia: Recapitulating the human disease. Blood. 2017;129:2217–2223. doi: 10.1182/blood-2016-10-691428. - DOI - PMC - PubMed

[7] Li H., Auwerx J. Mouse Systems Genetics as a Prelude to Precision Medicine. Trends Genet. 2020;36:259–272. doi: 10.1016/j.tig.2020.01.004. - DOI - PMC - PubMed

[8] Li H., Auwerx J. Mouse Systems Genetics as a Prelude to Precision Medicine. Trends Genet. 2020;36:259–272. doi: 10.1016/j.tig.2020.01.004. - DOI - PMC - PubMed

[9] Tadenev A.L.D., Burgess R.W. Model validity for preclinical studies in precision medicine: Precisely how precise do we need to be? Mamm. Genome. 2019;30:111–122. doi: 10.1007/s00335-019-09798-0. - DOI - PMC - PubMed

[10] Tadenev A.L.D., Burgess R.W. Model validity for preclinical studies in precision medicine: Precisely how precise do we need to be? Mamm. Genome. 2019;30:111–122. doi: 10.1007/s00335-019-09798-0. - DOI - PMC - PubMed

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Modeling Rare Human Disorders in Mice: The Finnish Disease Heritage

Affiliations

Modeling Rare Human Disorders in Mice: The Finnish Disease Heritage

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Affiliations

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Conflict of interest statement

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