Molecular Characterization of Novel FOXN1 Mutations Causal to Thymic Aplasias in Human Patients

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dc.contributor.otherDu, Qiumeien
dc.contributor.otherKhan, Shaheenen
dc.contributor.otherMolina, Erikaen
dc.contributor.otherPadron, Grace T.en
dc.contributor.otherMarkert, M. Louiseen
dc.contributor.otherde la Morena, Maria Teresaen
dc.contributor.othervan Oers, Nicolaien
dc.creatorHuynh, Larryen
dc.creator.orcid0000-0002-1492-5931
dc.date.accessioned2018-06-06T23:48:22Z
dc.date.available2018-06-06T23:48:22Z
dc.date.issued2018-01-23
dc.descriptionThe 56th Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 23, 2018, 2-5 p.m., D1.600)en
dc.description.abstractThe Forkhead Box N1 (FOXN1) transcription factor plays a crucial role in thymic epithelial cell development. Humans and mice harboring FOXN1 mutations have a profound T-cell deficiency caused by their thymic aplasia. They also present with alopecia and nail dystrophy. Recently, two patients were identified with T-cell immunodeficiency. Both patients have normal hair and nailbed development. Genetic workup revealed that each patient carried distinct compound heterozygous mutations in FOXN1 not previously reported. Molecular characterization of these FOXN1 mutations will provide new insight into how this transcription factor functions in thymus development. To characterize these mutations, CRISPR/Cas9 technologies were used to create similar compound heterozygous mutations in mouse models. The mice are currently being intercrossed to determine the impact of these novel FOXN1 mutations on thymus development. To determine how these mutations impact FOXN1 function, we undertook transcriptional reporter assays. Preliminary results suggest only one of these mutations led to loss of transcriptional activity. Western blot analysis indicated that this mutation led to a truncation of the protein. Further experiments including co-immunoprecipitation assays, transcriptome analyses, and functional studies will reveal how these compound heterozygous mutations impact the functions of FOXN1. Findings from this study may lay the foundation for novel therapeutic strategies at restoring thymopoiesis in a number of distinct clinical settings. These can include patients undergoing radiation treatment, chemotherapy, and in any other conditions that can lead to a thymic aplasia.en
dc.description.sponsorshipSouthwestern Medical Foundationen
dc.identifier.citationHuynh, L, Du, Q., Khan, S., Molina E., Padron, G. T., Markert, M. L., . . . van Oers, N. (2018, January 23). Molecular characterization of novel FOXN1 mutations causal to thymic aplasias in human patients. Poster session presented at the 56th Annual Medical Student Research Forum, Dallas, TX. Retrieved from https://hdl.handle.net/2152.5/5319en
dc.identifier.urihttps://hdl.handle.net/2152.5/5319
dc.language.isoenen
dc.relation.ispartofseries56th Annual Medical Student Research Forumen
dc.subjectBasic Research and Disease Modelsen
dc.subject.meshForkhead Transcription Factorsen
dc.subject.meshImmunologic Deficiency Syndromesen
dc.subject.meshMutationen
dc.subject.meshThymus Glanden
dc.titleMolecular Characterization of Novel FOXN1 Mutations Causal to Thymic Aplasias in Human Patientsen
dc.typePresentationen

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