{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:14:57Z","timestamp":1791339297735,"version":"4.3.1"},"reference-count":50,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T00:00:00Z","timestamp":1638662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["RGPIN-2019-07076"],"award-info":[{"award-number":["RGPIN-2019-07076"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-153264"],"award-info":[{"award-number":["PJT-153264"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hirschsprung disease is a congenital malformation where ganglia of the neural crest-derived enteric nervous system are missing over varying lengths of the distal gastrointestinal tract. This complex genetic condition involves both rare and common variants in dozens of genes, many of which have been functionally validated in animal models. Modifier loci present in the genetic background are also believed to influence disease penetrance and severity, but this has not been frequently tested in animal models. Here, we addressed this question using Holstein mice in which aganglionosis is due to excessive deposition of collagen VI around the developing enteric nervous system, thereby allowing us to model trisomy 21-associated Hirschsprung disease. We also asked whether the genetic background might influence the response of Holstein mice to GDNF enemas, which we recently showed to have regenerative properties for the missing enteric nervous system. Compared to Holstein mice in their original FVB\/N genetic background, Holstein mice maintained in a C57BL\/6N background were found to have a less severe enteric nervous system defect and to be more responsive to GDNF enemas. This change of genetic background had a positive impact on the enteric nervous system only, leaving the neural crest-related pigmentation phenotype of Holstein mice unaffected. Taken together with other similar studies, these results are thus consistent with the notion that the enteric nervous system is more sensitive to genetic background changes than other neural crest derivatives.<\/jats:p>","DOI":"10.3390\/ijms222313140","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T21:01:45Z","timestamp":1638738105000},"page":"13140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genetic Background Influences Severity of Colonic Aganglionosis and Response to GDNF Enemas in the Holstein Mouse Model of Hirschsprung Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Rodolphe","family":"Soret","sequence":"first","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montr\u00e9al, QC H3C 3P8, Canada"},{"name":"Centre D\u2019excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO-FC), Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, QC H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nejia","family":"Lassoued","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montr\u00e9al, QC H3C 3P8, Canada"},{"name":"Centre D\u2019excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO-FC), Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, QC H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9goire","family":"Bonnamour","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montr\u00e9al, QC H3C 3P8, Canada"},{"name":"Centre D\u2019excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO-FC), Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, QC H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-5732","authenticated-orcid":false,"given":"Guillaume","family":"Bernas","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montr\u00e9al, QC H3C 3P8, Canada"},{"name":"Centre D\u2019excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO-FC), Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, QC H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Barbe","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montr\u00e9al, QC H3C 3P8, Canada"},{"name":"Centre D\u2019excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO-FC), Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, QC H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montr\u00e9al, QC H3C 3P8, Canada"},{"name":"Centre D\u2019excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO-FC), Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, QC H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Aichi","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montr\u00e9al, QC H3C 3P8, Canada"},{"name":"Centre D\u2019excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO-FC), Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, QC H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3641-0776","authenticated-orcid":false,"given":"Nicolas","family":"Pilon","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montr\u00e9al, QC H3C 3P8, Canada"},{"name":"Centre D\u2019excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO-FC), Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, QC H2X 3Y7, Canada"},{"name":"D\u00e9partement de P\u00e9diatrie, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/nrgastro.2017.149","article-title":"Hirschsprung disease\u2014Integrating basic science and clinical medicine to improve outcomes","volume":"15","author":"Heuckeroth","year":"2018","journal-title":"Nat. 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