In this video collection, authors of findings published in The Journal of Clinical Investigation present personally guided tours of their results. The journal accepts video submissions from authors of recently accepted manuscripts. Instructions can be found on the Author's Take Guidelines page.
In this episode, Nicolai van Oers and colleagues demonstrate that compound heterozygous mutations in FOXN1 result in a combined immunodeficiency in patients that is distinct Nude/SCID phenotypes.
In this episode, Tamás Röszer and colleagues demonstrate that breast-milk-derived alkylglycerols preserve beige adipocytes to protect against obesity.
The transcription factor GATA-2 is critical regulator of hematopoietic stem and progenitor cell (HSPC) development and function, and mutations in the enhancer region of GATA2 are linked to blood disorders. In this episode, Emery Bresnick and colleagues develop and characterize a mouse model that harbors a human disease-associated GATA2 enhancer mutation. In this model, hematopoietic development and function were normal unless the animals were exposed to a secondary stress that necessitated blood cell regeneration. The results of this study provide important insight into GATA-2-dependent pathogenesis.
Achromatopsia is form of congenital retinal degeneration characterized by the loss of cone photoreceptor function, resulting in dramatic loss of visual acuity. Mouse models of cone disorders are available; however, clinical translation of these models is limited, as cone density in the murine retina is much less than that of humans. In this episode, Sara Thomasy and Ala Moshiri discuss the identification and characterization of a naturally occurring mutation in nonhuman primates that results in features that mirror human achromatopsia. This nonhuman primate model has high potential for therapeutic testing and optimization of gene editing and of cone cell replacement strategies.
Leukodystrophies are rare congenital disorders that affect the white matter of the brain, resulting in a range of neurological presentations. Several leukodystrophy-associated genes have been identified; however, the etiology of many cases remains unclear. In this episode, Aurora Pujol, Ali Fatemi, Marc Patterson, Javier Terriente, and Carlos Casasnovas discuss their collaboration, which led to the identification of a mutation in the endoplasmic reticulum lipid desaturase DEGS1 as the underlying cause of a leukodystrophy in 19 patients from 13 unrelated families. The mutation was linked to an imbalance of the DEGS1 substrate dihydroceramide and ceramide. In a DEGS1 knockdown zebrafish model, treatment with fingolimod reduced the imbalance between dihydroceramide and ceramide, decreased locomotor disability, and increased oligodendrocyte myelination, suggesting this strategy be explored for mutant DESG1-related disease.