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Ideally, models achieve both, but this is not always possible; nonetheless, such models are informative. Here we describe two animal models of inherited peripheral neuropathy: mice with a mutation in tyrosyl tRNA\u2010synthetase,\n                    <jats:italic>Yars<\/jats:italic>\n                    <jats:sup>E196K<\/jats:sup>\n                    , modeling dominant intermediate Charcot\u2010Marie\u2010Tooth disease type C (diCMTC), and mice with a mutation in serine palmitoyltransferase long chain 1,\n                    <jats:italic>Sptlc1<\/jats:italic>\n                    <jats:sup>C133W<\/jats:sup>\n                    , modeling hereditary sensory and autonomic neuropathy type 1 (HSAN1).\n                    <jats:italic>Yars<\/jats:italic>\n                    <jats:sup>E196K<\/jats:sup>\n                    mice develop disease\u2010relevant phenotypes including reduced motor performance and reduced nerve conduction velocities by 4\u00a0months of age. Peripheral motor axons are reduced in size, but there is no reduction in axon number and plasma neurofilament light chain levels are not increased. Unlike the dominant human mutations, the\n                    <jats:italic>Yars<\/jats:italic>\n                    <jats:sup>E196K<\/jats:sup>\n                    mice only show these phenotypes as homozygotes, or as compound heterozygotes with a null allele, and no phenotype is observed in E196K or null heterozygotes. The\n                    <jats:italic>Sptlc1<\/jats:italic>\n                    <jats:sup>C133W<\/jats:sup>\n                    mice carry a knockin allele and show the anticipated increase in 1\u2010deoxysphingolipids in circulation and in a variety of tissues. They also have mild behavioral defects consistent with HSAN1, but do not show neurophysiological defects or axon loss in peripheral nerves or in the epidermis of the hind paw or tail. Thus, despite the biochemical phenotype, the\n                    <jats:italic>Sptlc1<\/jats:italic>\n                    <jats:sup>C133W<\/jats:sup>\n                    mice do not show a strong neuropathy phenotype. Surprisingly, these mice were lethal as homozygotes, but the heterozygous genotype studied corresponds to the dominant genetics seen in humans. Thus,\n                    <jats:italic>Yars<\/jats:italic>\n                    <jats:sup>E196K<\/jats:sup>\n                    homozygous mice have a relevant phenotype, but imprecisely reproduce the human genetics, whereas the\n                    <jats:italic>Sptlc1<\/jats:italic>\n                    <jats:sup>C133W<\/jats:sup>\n                    mice precisely reproduce the human genetics, but do not recreate the disease phenotype. Despite these shortcomings, both models are informative and will be useful for future research.\n                  <\/jats:p>","DOI":"10.1111\/joa.13605","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T19:50:28Z","timestamp":1638906628000},"page":"1169-1185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Precision mouse models of\n                    <i>Yars<\/i>\n                    \/dominant intermediate Charcot\u2010Marie\u2010Tooth disease type C and\n                    <i>Sptlc1<\/i>\n                    \/hereditary sensory and autonomic neuropathy type 1"],"prefix":"10.1111","volume":"241","author":[{"given":"Timothy J.","family":"Hines","sequence":"first","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail L. D.","family":"Tadenev","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Museer A.","family":"Lone","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney L.","family":"Hatton","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inseyah","family":"Bagasrawala","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane G.","family":"Stum","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy E.","family":"Miers","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Hornemann","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-3407","authenticated-orcid":false,"given":"Robert W.","family":"Burgess","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine 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