Immunodeficiency: primary or acquired

Oral

Hypoplastic Thymii from Mouse Models of digeorge-22q11.2 Deletion Syndrome Have a Signature Gene Expression Pattern

Friday, June 16
6:15 PM - 7:30 PM

Chromosome 22q11.2 deletion syndrome (22q11.2 DS) is the most frequent chromosomal microdeletion disorder reported (1/4000). Individuals with this deletion often present with multi-system disorders including a thymic hypoplasia, cardiac anomalies, hypoparathyroidism, and/or dysmorphic facial features. Over 90% of individuals have a deletion of 2.4 Mb, which comprises 90 genes, 50% protein coding and the remainder microRNAs, long noncoding RNAs and pseudogenes. The principal cause of the development defects is a haploinsufficiency of T-box 1 transcription factor (Tbx1). Between 40-60% of patients have some degree of thymic hypoplasia, resulting in their peripheral T cell lymphopenia. Defects in the thymic stromal tissue is the underlying cause of the hypoplasia. We analyzed the thymic tissue in a mouse models of 22q11.2 deletion syndrome, termed the Df1/+ line. Comparative transcriptome analyses of hypoplastic and normal-sized lobes from matched Df1/+ embryos revealed a signature mRNA expression pattern unique to hypoplastic tissue. Ingenuity pathway analysis uncovered selective pathways compromised in these lobes. Immunohistochemistry and fetal thymic organ culture assays are currently being used to characterize the molecular defects of the thymic stroma at the onset of thymic tissue specification in embryos. Inflammatory conditions are being introduced in pregnant Df1/+ mice to determine if the penetrance and severity of clinical phenotypes associated with 22q11.2 DS is affected by stress in utero. Findings from our studies may lead to better strategies for improving human thymopoiesis, particularly for patients with 22q11.2 and 10p deletion syndromes, as well as those undergoing chemo ablative treatments that impact the thymus.

Nicolai S.C.. van Oers

Associate Professor
UT Southwestern Medical Ctr

Presentation(s):

    Send Email for Nicolai van Oers

    Qiumei Du

    Post-doctoral fellow
    UT Southwestern Medical Center

    Presentation(s):

      Send Email for Qiumei Du

      M. Teresa de la Morena

      Professor
      UT Southwestern Medical Center

      Presentation(s):

        Send Email for M. Teresa de la Morena

        Igor Dozmorov

        Associate Professor
        UT Southwestern Medical Center

        Presentation(s):

          Send Email for Igor Dozmorov

          Shaheen Khan

          Instructor
          UT Southwestern Medical Center

          Presentation(s):

            Send Email for Shaheen Khan

            Ondine B. Cleaver

            Associate Professor
            UT Southwestern Medical Center

            Presentation(s):

              Send Email for Ondine Cleaver


              Assets

              Hypoplastic Thymii from Mouse Models of digeorge-22q11.2 Deletion Syndrome Have a Signature Gene Expression Pattern



              Attendees who have favorited this

              Send Email for Hypoplastic Thymii from Mouse Models of digeorge-22q11.2 Deletion Syndrome Have a Signature Gene Expression Pattern