caa a22 4500 397574290 CHVBK 20180308164850.0 cr unu---uuuuu 161202e199601 xx s 000 0 eng 10.1093/hmg/5.1.85 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.1.85 Developmental Expression of the Fac Gene Correlates with Congenital Defects in Fanconi Anemia Patients [Elektronische Daten] [Flora Krasnoshtein, Manuel Buchwald] Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by a variety of congenital and skeletal malformations, progressive pancytopaenia and predisposition to malignancies. While the basic defect in this disease is not known, the cloning of the gene defective in FA group C patients (FAC) allows analysis of its expression pattern, which may provide clues about the functional properties of the protein. This paper describes the distribution of Fac transcripts during murine development (8-19.5 days p.c.), using RNA in situ hybridization. Fac is initially expressed (8-10 days p.c.) in the mesenchyme and its derivatives with osteogenic potential. The transcript is also apparent at later stages of bone development (13-19.5 days p.c.), localized to cells of the inner perichondrium, periosteum and zone of endochondral ossification. In the latter, Fac transcripts are seen in cells from both osteogenic and hematopoietic lineages. Fac mRNA is also seen in intramembranous cranial and facial bones. In addition, Fac signal is detected in non-skeletal tissues: brain, whisker follicles, lung, kidney, gut and stomach. Fac expression is high in progenitor cell populations but is downregulated in differentiating cells that give rise to connective tissue. The pattern of Fac expression is consistent with the skeletal and non-skeletal congenital abnormalities in FA patients. As well, expression in rapidly dividing progenitors is consistent with hypotheses regarding the nature of the basic defect in FA: a role of the protein in DNA repair or protection from oxygen toxicity. © 1996 Oxford University Press Krasnoshtein Flora Research Institute, Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1X8, Canada aut Buchwald Manuel Research Institute, Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1X8, Canada aut Human Molecular Genetics Oxford University Press 5/1(1996-01), 85-93 0964-6906 5:1<85 1996 5 hmg https://doi.org/10.1093/hmg/5.1.85 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.1.85 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Krasnoshtein Flora Research Institute, Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1X8, Canada aut NATIONALLICENCE 700 1- Buchwald Manuel Research Institute, Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1X8, Canada aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/1(1996-01), 85-93 0964-6906 5:1<85 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford