Journal article

Rothmund-Thomson Syndrome-Like RECQL4 Truncating Mutations Cause a Haploinsufficient Low-Bone-Mass Phenotype in Mice

Wilson Castillo-Tandazo, Ann E Frazier, Natalie A Sims, Monique F Smeets, Carl R Walkley

MOLECULAR AND CELLULAR BIOLOGY | AMER SOC MICROBIOLOGY | Published : 2021

Abstract

Rothmund-Thomson Syndrome (RTS) is an autosomal recessive disorder characterized by defects in the skeletal system such as bone hypoplasia, short stature, low bone mass, and an increased incidence of osteosarcoma. RTS type 2 patients have germline compound bi-allelic protein-truncating mutations of RECQL4 As existing murine models employ Recql4 null alleles, we have attempted to more accurately model RTS by generating mice with patient-mimicking truncating Recql4 mutations. Truncating mutations impaired the stability and subcellular localization of RECQL4, and resulted in homozygous embryonic lethality and a haploinsufficient low bone mass phenotype. Combination of a truncating mutation with..

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Grants

Awarded by Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Cancer Research


Awarded by National Health and Medical Research Council (NHMRC) Australia


Awarded by Victorian Cancer Agency research fellowship


Funding Acknowledgements

This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Cancer Research under award no. W81XWH-15-10315 (to C.R.W.). Funding also came fromthe National Health and Medical Research Council (NHMRC) Australia project grant (to C.R.W.; APP1102004); a Melbourne Research Scholarship (to W.C.-T.; University of Melbourne); a Victorian Cancer Agency research fellowship (to CRW, MCRF15015); and the Mito Foundation (to A.E.F.). This work was enabled by the Australian Phenomics Network and partly supported by funding from the Australian government's National Collaborative Research Infrastructure Strategy and the Super Science Initiative through the Education Investment Fund (to the Australian Phenomics Network) and in part supported by the Victorian State Government Operational Infrastructure Support (to St. Vincent's Institute and the Murdoch Children's Research Institute).