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On the DBA\/2J-, but not on the C57BL\/6J-background, <jats:italic>Lyst<\/jats:italic>-mutant mice exhibit overt tremor phenotypes associated with loss of cerebellar Purkinje cells. Here, we tested whether assays for ataxia could measure this observed strain-dependency, and if so, establish parameters for empowering phenotype- and candidate-driven approaches to identify genetic modifier(s). A composite phenotypic scoring system distinguished phenotypes in <jats:italic>Lyst<\/jats:italic>-mutants and uncovered a previously unrecognized background difference between wild-type C57BL\/6J and DBA\/2J mice. Accelerating rotarod performance also distinguished phenotypes in <jats:italic>Lyst<\/jats:italic>-mutants, but at more advanced ages. These results establish that genetic background, <jats:italic>Lyst<\/jats:italic> genotype, and age significantly influence the severity of CHS-associated neurologic deficits. Purkinje cell quantifications likewise distinguished phenotypes of <jats:italic>Lyst<\/jats:italic>-mutant mice, as well as background differences between wild-type C57BL\/6J and DBA\/2J mice. To aid identification of potential genetic modifier genes causing these effects, we searched public datasets for cerebellar-expressed genes that are differentially expressed and\/or contain potentially detrimental genetic variants. From these approaches, <jats:italic>Nos1<\/jats:italic>, <jats:italic>Prdx<\/jats:italic>2, <jats:italic>Cbln3<\/jats:italic>, <jats:italic>Gnb1<\/jats:italic>, <jats:italic>Pttg1<\/jats:italic> were confirmed to be differentially expressed and leading candidates.<\/jats:p>","DOI":"10.1038\/s41598-019-42159-0","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T10:02:54Z","timestamp":1556704974000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mouse models and strain-dependency of Ch\u00e9diak-Higashi syndrome-associated neurologic dysfunction"],"prefix":"10.1038","volume":"9","author":[{"given":"Adam","family":"Hedberg-Buenz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"Dutca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demelza R.","family":"Larson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kacie J.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana A.","family":"Soukup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carly J.","family":"van der Heide","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah E.","family":"Mercer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael G.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,5,1]]},"reference":[{"key":"42159_CR1","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1055\/s-0037-1616221","volume":"86","author":"M Huizing","year":"2001","unstructured":"Huizing, M., Anikster, Y. & Gahl, W. A. Hermansky-Pudlak syndrome and Chediak-Higashi syndrome: disorders of vesicle formation and trafficking. Thromb Haemost 86, 233\u2013245 (2001).","journal-title":"Thromb Haemost"},{"key":"42159_CR2","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1097\/MOH.0b013e3282f2bcce","volume":"15","author":"J Kaplan","year":"2008","unstructured":"Kaplan, J., De Domenico, I. & Ward, D. M. Chediak-Higashi syndrome. Curr Opin Hematol 15, 22\u201329, https:\/\/doi.org\/10.1097\/MOH.0b013e3282f2bcce (2008).","journal-title":"Curr Opin Hematol"},{"key":"42159_CR3","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1034\/j.1600-0749.2002.02038.x","volume":"15","author":"SL Shiflett","year":"2002","unstructured":"Shiflett, S. L., Kaplan, J. & Ward, D. M. Chediak-Higashi Syndrome: a rare disorder of lysosomes and lysosome related organelles. 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