H19 and Igf2 are closely linked, reciprocally imprinted genes which lie on distal chromosome 7 in the mouse. Data suggests that common elements are used for expression and imprinting of both genes, and simple models have been proposed based on the presence of a single set of enhancers located downstream of H19. In this study we have investigated the H19 expression pattern from a 130 kb YAC tran...

Apert syndrome is an autosomal dominant disorder characterized by malformations of the skull, limbs and viscera. Two-thirds of affected individuals have a S252W mutation in fibroblast growth factor receptor 2 (FGFR2). To study the pathogenesis of this condition, we generated a knock-in mouse model with this mutation. The Fgfr2(+/S252W) mutant mice have abnormalities of the skeleton, as well as ...

A new type of murine leukemia virus has been detected in thymuses of leukemic and late preleukemic AKR mice, in lymphomas developing in NIH Swiss mice carrying the AKR ectopic virus-inducing loci Akv-I or Akv-2, and in the thymus of a preleukemic C58 mouse. The viruses induce focal areas of morphologic alteration in a mink lung cell line and are tentatively referred to as "mink cell focus-induc...

A subcutaneous mass in the left supraclavicular fossa of a 55-year-old woman proved on histological examination to be composed of islands of squamous cells embedded in bands of spindle cells and associated with mature adipose tissue. Electron microscopy showed that the spindle cells were fibroblastic in nature and not squamous cells showing spindle differentiation. There was also a minor lympha...

The clinical case described in this paper deals with a young female patient affected by primary hyperparathyroidism caused by an ectopic parathyroid adenoma of a supernumerary intrathymic parathyroid. The patient had hypercalcemia, in association with increased levels of parathormone, but was otherwise asymptomatic. Genetics tests for mutation of the MEN1, HRPT2, and CaSR genes were negative. S...

Mutations in the transcriptional regulator, Aire, cause APECED, a polyglandular autoimmune disease with monogenic transmission. Animal models of APECED have revealed that Aire plays an important role in T cell tolerance induction in the thymus, mainly by promoting ectopic expression of a large repertoire of transcripts encoding proteins normally restricted to differentiated organs residing in t...

The E2A transcription factors promote the development of thymus-seeding cells, but it remains unknown whether these proteins play a role in T lymphocyte lineage specification or commitment. Here, we showed that E2A proteins were required to promote T-lymphocyte commitment from DN2 thymocytes and to extinguish their potential for alternative fates. E2A proteins functioned in DN2 cells to limit e...

In order to gain novel insights into thymus biology, we analysed the whole transcriptome of cortical and medullary thymic epithelial cells (cTECs and mTECs) and of skin epithelial cells (ECs). Consistent with their ability to express ectopic genes, mTECs expressed more genes than other cell populations. Out of a total of 15,069 genes expressed in TECs, 25% were differentially expressed by at le...

Drosophila neural stem cells (neuroblasts) are a powerful model system for investigating stem cell self-renewal, specification of temporal identity, and progressive restriction in competence. Notch signaling is a conserved cue that is an important determinant of cell fate in many contexts across animal development; for example, mammalian T cell differentiation in the thymus and neuroblast speci...

TBX1 is a principal candidate gene for DiGeorge syndrome, a developmental anomaly that affects the heart, thymus, parathyroid, face, and teeth. A mouse model carrying a deletion in a functional region of the Tbx1 gene has been extensively used to study anomalies related to this syndrome. We have used the Tbx1 null mouse to understand the tooth phenotype reported in patients afflicted by DiGeorg...