Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1)
Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a co-chaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2015-11-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/8/11/1457 |
| _version_ | 1818826359997202432 |
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| author | Flavio H. Beraldo Anu Thomas Benjamin Kolisnyk Pedro H. Hirata Xavier De Jaeger Amanda C. Martyn Jue Fan Daniela F. Goncalves Matthew F. Cowan Talal Masood Vilma R. Martins Robert Gros Vania F. Prado Marco A. M. Prado |
| author_facet | Flavio H. Beraldo Anu Thomas Benjamin Kolisnyk Pedro H. Hirata Xavier De Jaeger Amanda C. Martyn Jue Fan Daniela F. Goncalves Matthew F. Cowan Talal Masood Vilma R. Martins Robert Gros Vania F. Prado Marco A. M. Prado |
| author_sort | Flavio H. Beraldo |
| collection | DOAJ |
| description | Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a co-chaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test for potential ASD-like phenotypes. We found that increased STIP1 regulates the abundance of Hsp70 and Hsp90, whereas reduced STIP1 does not affect Hsp70, Hsp90 or the prion protein. Interestingly, BAC transgenic mice presenting fivefold more STIP1 show no major phenotype when examined in a series of behavioral tasks, including locomotor activity, elevated plus maze, Morris water maze and five-choice serial reaction time task (5-CSRTT). In contrast, mice with reduced STIP1 levels are hyperactive and have attentional deficits on the 5-CSRTT, but exhibit normal performance for the other tasks. We conclude that reduced STIP1 levels can contribute to phenotypes related to ASD. However, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes. |
| first_indexed | 2024-12-19T00:26:25Z |
| format | Article |
| id | doaj.art-d92dfd7a39ac4bbfa533c0c083604adc |
| institution | Directory Open Access Journal |
| issn | 1754-8411 1754-8403 |
| language | English |
| last_indexed | 2024-12-19T00:26:25Z |
| publishDate | 2015-11-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-d92dfd7a39ac4bbfa533c0c083604adc2022-12-21T20:45:14ZengThe Company of BiologistsDisease Models & Mechanisms1754-84111754-84032015-11-018111457146610.1242/dmm.022525022525Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1)Flavio H. Beraldo0Anu Thomas1Benjamin Kolisnyk2Pedro H. Hirata3Xavier De Jaeger4Amanda C. Martyn5Jue Fan6Daniela F. Goncalves7Matthew F. Cowan8Talal Masood9Vilma R. Martins10Robert Gros11Vania F. Prado12Marco A. M. Prado13 Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Department of Molecular and Cell Biology, International Research Center, A.C. Camargo Cancer Center and National Institute for Translational Neuroscience Research Center, Sao Paulo, SP 01508-010, Brazil Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Robarts Research Institute, The University of Western Ontario, London, Ontario N6A5B7, Canada Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a co-chaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test for potential ASD-like phenotypes. We found that increased STIP1 regulates the abundance of Hsp70 and Hsp90, whereas reduced STIP1 does not affect Hsp70, Hsp90 or the prion protein. Interestingly, BAC transgenic mice presenting fivefold more STIP1 show no major phenotype when examined in a series of behavioral tasks, including locomotor activity, elevated plus maze, Morris water maze and five-choice serial reaction time task (5-CSRTT). In contrast, mice with reduced STIP1 levels are hyperactive and have attentional deficits on the 5-CSRTT, but exhibit normal performance for the other tasks. We conclude that reduced STIP1 levels can contribute to phenotypes related to ASD. However, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes.http://dmm.biologists.org/content/8/11/1457TouchscreenAutismASDStress-inducible phosphoprotein 1Attention deficitsMouse modelBAC |
| spellingShingle | Flavio H. Beraldo Anu Thomas Benjamin Kolisnyk Pedro H. Hirata Xavier De Jaeger Amanda C. Martyn Jue Fan Daniela F. Goncalves Matthew F. Cowan Talal Masood Vilma R. Martins Robert Gros Vania F. Prado Marco A. M. Prado Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1) Disease Models & Mechanisms Touchscreen Autism ASD Stress-inducible phosphoprotein 1 Attention deficits Mouse model BAC |
| title | Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1) |
| title_full | Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1) |
| title_fullStr | Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1) |
| title_full_unstemmed | Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1) |
| title_short | Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1) |
| title_sort | hyperactivity and attention deficits in mice with decreased levels of stress inducible phosphoprotein 1 stip1 |
| topic | Touchscreen Autism ASD Stress-inducible phosphoprotein 1 Attention deficits Mouse model BAC |
| url | http://dmm.biologists.org/content/8/11/1457 |
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