color:#003366">Dr. Henk Granzier awarded $1.7 million by NIH to study the Roles of Nebulin in Structure and Function of Straited Muscle

color:#003366">

Calibri;mso-fareast-theme-font:minor-latin;color:#333333;mso-ansi-language:
EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA">Dr. Henk Granzier, Professor of Physiology at the University Of Arizona College Of Medicine has been awarded a $1.7 million 5 year grant by the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases to study the roles of Nebulin in structure and function of striated muscle.

Nebulin is a giant filamentous protein found in the sarcomere (contractile unit) of skeletal muscle.  Nebulin plays structural roles, and in addition Dr. Granzier has recently shown that it is also crucial in muscle contraction.  This is an exciting concept not only because it reveals a previously unknown major aspect of skeletal muscle physiology, but also because it helps to explain why nemaline myopathy (NM) patients with nebulin deficiency have severe muscle weakness.  The role of nebulin in muscle contraction will be examined in the newly funded award.  A large group of NM patients has nebulin deficiency that results from an in-frame deletion of nebulin’s exon 55, and a novel mouse disease model was made in which exon 55 (NEB Δex55) has been deleted.  The funded work will determine the functional properties of this model at the intact muscle, skinned fiber, and myofibrillar levels and compare results to those on biopsies from NM patients.  To gain insights into therapies that augment contractile strength in nebulin-deficient skeletal muscle (mouse model and NM patients) the effects of a novel class of calcium sensitizers will be studied.