{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:03:57Z","timestamp":1792047837869,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T00:00:00Z","timestamp":1692403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ataxia Canada","award":["130852"],"award-info":[{"award-number":["130852"]}]},{"name":"Ataxia Canada","award":["418059"],"award-info":[{"award-number":["418059"]}]},{"name":"Ataxia Canada","award":["91977"],"award-info":[{"award-number":["91977"]}]},{"name":"Canadian Institute of Health Research","award":["130852"],"award-info":[{"award-number":["130852"]}]},{"name":"Canadian Institute of Health Research","award":["418059"],"award-info":[{"award-number":["418059"]}]},{"name":"Canadian Institute of Health Research","award":["91977"],"award-info":[{"award-number":["91977"]}]},{"name":"Th\u00e9Cell FRQS network","award":["130852"],"award-info":[{"award-number":["130852"]}]},{"name":"Th\u00e9Cell FRQS network","award":["418059"],"award-info":[{"award-number":["418059"]}]},{"name":"Th\u00e9Cell FRQS network","award":["91977"],"award-info":[{"award-number":["91977"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by a GAA repeat in the intron 1 of the frataxin gene (FXN) leading to a lower expression of the frataxin protein. The YG8sR mice are Knock-Out (KO) for their murine frataxin gene but contain a human frataxin transgene derived from an FRDA patient with 300 GAA repeats. These mice are used as a FRDA model but even with a low frataxin concentration, their phenotype is mild. We aimed to find an optimized mouse model with a phenotype comparable to the human patients to study the impact of therapy on the phenotype. We compared two mouse models: the YG8sR injected with an AAV. PHP.B coding for a shRNA targeting the human frataxin gene and the YG8-800, a new mouse model with a human transgene containing 800 GAA repeats. Both mouse models were compared to Y47R mice containing nine GAA repeats that were considered healthy mice. Behavior tests (parallel rod floor apparatus, hanging test, inverted T beam, and notched beam test) were carried out from 2 to 11 months and significant differences were noticed for both YG8sR mice injected with an anti-FXN shRNA and the YG8-800 mice compared to healthy mice. In conclusion, YG8sR mice have a slight phenotype, and injecting them with an AAV-PHP.B expressing an shRNA targeting frataxin does increase their phenotype. The YG8-800 mice have a phenotype comparable to the human ataxic phenotype.<\/jats:p>","DOI":"10.3390\/genes14081654","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T01:38:31Z","timestamp":1692581911000},"page":"1654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Finding an Appropriate Mouse Model to Study the Impact of a Treatment for Friedreich Ataxia on the Behavioral Phenotype"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-4090","authenticated-orcid":false,"given":"Camille","family":"Bouchard","sequence":"first","affiliation":[{"name":"Centre de Recherche du CHU, Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"D\u00e9partement de M\u00e9decine Mol\u00e9culaire, l\u2019Universit\u00e9 Laval Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"G\u00e9rard","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU, Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"D\u00e9partement de M\u00e9decine Mol\u00e9culaire, l\u2019Universit\u00e9 Laval Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solange Gni-fiene","family":"Yanyab\u00e9","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU, Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"D\u00e9partement de M\u00e9decine Mol\u00e9culaire, l\u2019Universit\u00e9 Laval Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Majeau","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU, Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"D\u00e9partement de M\u00e9decine Mol\u00e9culaire, l\u2019Universit\u00e9 Laval Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malek","family":"Aloui","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU, Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Buisson","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU, Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-8297","authenticated-orcid":false,"given":"Pouir\u00e9","family":"Yameogo","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU, Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"D\u00e9partement de M\u00e9decine Mol\u00e9culaire, l\u2019Universit\u00e9 Laval Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Couture","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU, Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"D\u00e9partement de M\u00e9decine Mol\u00e9culaire, l\u2019Universit\u00e9 Laval Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9404-9195","authenticated-orcid":false,"given":"Jacques P.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU, Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"D\u00e9partement de M\u00e9decine Mol\u00e9culaire, l\u2019Universit\u00e9 Laval Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1089\/nat.2017.0703","article-title":"Activation of frataxin protein expression by antisense oligonucleotides targeting the mutant expanded repeat","volume":"28","author":"Li","year":"2018","journal-title":"Nucleic Acid Ther."},{"key":"ref_2","first-page":"554","article-title":"The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia","volume":"59","author":"Filla","year":"1996","journal-title":"Am. 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