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Sarah Linn The Ohio State University The Jackson Laboratory – Bar Harbor, Maine From September 18 th to October 13 th , 2017, I was able to work for Dr. John Sundberg in his lab working on dermatopathology research at The Jackson Laboratory in Bar Harbor, Maine. Dr. Sundberg is well known in the field and knowledgeable about the various laboratory mouse strains. My project was a retrospective analysis of mouse nail slides within a previously published large scale aging study from 2007. This study looked at diseases of 30 aging mice strains from The Jackson Laboratory at 12 and 20 months and also during a longitudinal study. Dr. Sundberg noticed that the NON/ShiLtJ mice had a high prevalence of dystrophic nail lesions along with some other strains but at lower rate. He hoped to characterize the lesion further and kept the slides until Allison Mustonen and I came for our externships. Analysis of the slides showed nail dystrophy, subungual inflammation, remodeling of the distal phalanx, hyperplasia of the nail matrix and nail bed, and occasionally protrusion of the distal phalanx through the hyponychium. The lesions were also seen in the C57BR/cdJ, C57BL/6J, FVB/NJ, KK/H1J, MRL/MpJ, NZO/H1LtJ, NZW/LacJ, SM/J, and SWR/J strains. We gathered samples from younger NON/ShiLtJ breeders to see if the lesion was present at earlier ages which there were some mice that were affected. Complete analysis of the slides allowed us to propose a specific pathogenesis for this lesion which we are aiming to publish later this year. During the slide analysis, Allison and I discovered that about 40% of slides were not diagnostic for us to evaluate the nails. Mouse nails are hard to section because of their small size, varying tissues within the nail unit, and difficulty orienting the feet within paraffin. Our other project was to develop a better means of sectioning mouse nails in order to evaluate strains for phenotyping. We worked with the histology technicians at The Jackson Laboratory to see what fixatives and decalcification protocols would work best for sectioning. Starting with C57BL/6J females of the same age, we developed a protocol that worked well for sectioning the tissues, orienting the nails in wax, and immunohistochemical staining of the slides. We hope to publish our results after repeating the methods for various strains and males versus females. Aside from these projects, I attended the 16th Annual Workshop on the Pathology of Mouse Models of Human Disease. I was able to network with leaders in the field of mouse pathology and make valuable connections for my career. Allison and I also presented our work at the conference which was well received by the attendees. Overall, I had a valuable career experience with Dr. Sundberg. He was a great mentor throughout the externship and taught me what a veterinary pathologist can achieve at an institution like The Jackson Laboratory. I truly appreciate ACVP’s financial assistance for my externship and am thankful for the training I received.

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Page 1: ACVP - Jackson Laboratory Report - c.ymcdn.comc.ymcdn.com/.../Externship_Reports/ACVP_-_Jackson_Laboratory_Re.pdfwork for Dr. John Sundberg in his lab working on ... , and SWR/J strains

SarahLinnTheOhioStateUniversity

TheJacksonLaboratory–BarHarbor,Maine FromSeptember18thtoOctober13th,2017,IwasabletoworkforDr.JohnSundberginhislabworkingondermatopathologyresearchatTheJacksonLaboratoryinBarHarbor,Maine.Dr.Sundbergiswellknowninthefieldandknowledgeableaboutthevariouslaboratorymousestrains.Myprojectwasaretrospectiveanalysisofmousenailslideswithinapreviouslypublishedlargescaleaging

studyfrom2007.Thisstudylookedatdiseasesof30agingmicestrainsfromTheJacksonLaboratoryat12and20monthsandalsoduringalongitudinalstudy.Dr.SundbergnoticedthattheNON/ShiLtJmicehadahighprevalenceofdystrophicnaillesionsalongwithsomeotherstrainsbutatlowerrate.HehopedtocharacterizethelesionfurtherandkepttheslidesuntilAllisonMustonenandIcameforourexternships.Analysisoftheslidesshowednaildystrophy,subungualinflammation,remodelingofthedistalphalanx,hyperplasiaofthenailmatrixandnailbed,andoccasionallyprotrusionofthedistalphalanxthroughthehyponychium.ThelesionswerealsoseenintheC57BR/cdJ,C57BL/6J,FVB/NJ,KK/H1J,MRL/MpJ,NZO/H1LtJ,NZW/LacJ,SM/J,andSWR/Jstrains.WegatheredsamplesfromyoungerNON/ShiLtJbreederstoseeifthelesionwaspresentatearlierageswhichthereweresomemicethatwereaffected.Completeanalysisoftheslidesallowedustoproposeaspecificpathogenesisforthislesionwhichweareaimingtopublishlaterthisyear. Duringtheslideanalysis,AllisonandIdiscoveredthatabout40%ofslideswerenotdiagnosticforustoevaluatethenails.Mousenailsarehardtosectionbecauseoftheirsmallsize,varyingtissueswithinthenailunit,anddifficultyorientingthefeetwithinparaffin.Ourotherprojectwastodevelopabettermeansofsectioningmousenailsinordertoevaluatestrainsforphenotyping.WeworkedwiththehistologytechniciansatTheJacksonLaboratorytoseewhatfixativesanddecalcificationprotocolswouldworkbestforsectioning.StartingwithC57BL/6Jfemalesofthesameage,wedevelopedaprotocolthatworkedwellforsectioningthetissues,orientingthenailsinwax,andimmunohistochemicalstainingoftheslides.Wehopetopublishourresultsafterrepeatingthemethodsforvariousstrainsandmalesversusfemales. Asidefromtheseprojects,Iattendedthe16thAnnualWorkshoponthePathologyofMouseModelsofHumanDisease.Iwasabletonetworkwithleadersinthefieldofmousepathologyandmakevaluableconnectionsformycareer.AllisonandIalsopresentedourworkattheconferencewhichwaswellreceivedbytheattendees. Overall,IhadavaluablecareerexperiencewithDr.Sundberg.HewasagreatmentorthroughouttheexternshipandtaughtmewhataveterinarypathologistcanachieveataninstitutionlikeTheJacksonLaboratory.ItrulyappreciateACVP’sfinancialassistanceformyexternshipandamthankfulforthetrainingIreceived.

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