Journal article

Arrested Hematopoiesis and Vascular Relaxation Defects in Mice with a Mutation in Dhfr

Julie AI Thoms, Kathy Knezevic, Jia Jenny Liu, Elias N Glaros, Thuan Thai, Qiao Qiao, Heather Campbell, Deborah Packham, Yizhou Huang, Peter Papathanasiou, Robert Tunningley, Belinda Whittle, Amanda WS Yeung, Vashe Chandrakanthan, Luke Hesson, Vivien Chen, Jason WH Wong, Louise E Purton, Robyn L Ward, Shane R Thomas Show all

Molecular and Cellular Biology | AMER SOC MICROBIOLOGY | Published : 2016

Abstract

Dihydrofolate reductase (DHFR) is a critical enzyme in the folate metabolism pathway and also plays a role in regulating nitric oxide (NO) signaling in endothelial cells. Although both coding and noncoding mutations with phenotypic effects have been identified in the human DHFR gene, no mouse model is currently available to study the consequences of perturbing DHFR in vivo In order to identify genes involved in definitive hematopoiesis, we performed a forward genetic screen and produced a mouse line, here referred to as Orana, with a point mutation in the Dhfr locus leading to a Thr136Ala substitution in the DHFR protein. Homozygote Orana mice initiate definitive hematopoiesis, but expansion..

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Grants

Awarded by Australian Research Council (ARC)


Awarded by Department of Health | National Health and Medical Research Council (NHMRC)


Awarded by Cure Cancer Australia Foundation (CCAF)


Funding Acknowledgements

Anthony Rothe Memorial Trust provided funding to Julie A.I. Thoms. Department of Industry, Innovation, Science, Research and Tertiary Education, Australian Government | Australian Research Council (ARC) provided funding to Jason Wong under grant number FT13010096. Department of Health | National Health and Medical Research Council (NHMRC) provided funding to John E. Pimanda under grant numbers APP1102589 and APP1100495. Department of Health | National Health and Medical Research Council (NHMRC) provided funding to Shane R. Thomas under grant number APP1058508. Department of Health | National Health and Medical Research Council (NHMRC) provided funding to Elias N. Glaros under grant number APP1016847. Department of Health | National Health and Medical Research Council (NHMRC) provided funding to Louise E. Purton under grant number APP1003339. Cure Cancer Australia Foundation (CCAF) provided funding to Jason Wong under grant number APP1057921.Jia Jenny Liu was supported by an Australian Postgraduate Award and a Cancer Institute Research Scholars award. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.