Journal article

Dynll1 is essential for development and promotes endochondral bone formation by regulating intraflagellar dynein function in primary cilia

Ashleigh King, Nicolas C Hoch, Narelle E McGregor, Natalie A Sims, Ian M Smyth, Jorg Heierhorst

Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2019


Mutations in subunits of the cilia-specific cytoplasmic Dynein-2 (CD2) complex cause short-rib thoracic dystrophy syndromes (SRTDs), characterized by impaired bone growth and life-threatening perinatal respiratory complications. Different SRTD mutations result in varying disease severities. It remains unresolved whether this reflects the extent of retained hypomorphic protein functions or relative importance of the affected subunits for the activity of the CD2 holoenzyme. To define the contribution of the LC8-type dynein light chain subunit to the CD2 complex, we have generated Dynll1-deficient mouse strains, including the first-ever conditional knockout mutant for any CD2 subunit. Germline ..

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

Awarded by Australian Research Council

Funding Acknowledgements

National Health and Medical Research Council of Australia (NHMRC) (Senior Research Fellowship, GNT1022469, to J.H.; GNT1081242 to N.A.S.; Senior Research Fellowship, GNT1106516, and GNT1082051 and GNT1098654 to I.M.S.); the 5-point Foundation (to J.H.); the Margaret Walkom Bequest (to J.H.); an anonymous philantropic foundation (to J.H.); Australian Postgraduate Award to A.K.; SVU Brenda Shanahan Fellowship (to N.A.S.); Australian Research Council (DP160103100 to I.M.S.); and NHMRC Independent Research Institutes Infrastructure Support and Victorian State Government Operational Infrastructure Support grants.