Project description:Mutations in the gene encoding laminin a2 chain cause congenital muscular dystrophy, MDC1A. In skeletal muscle, laminin a2 chain binds at least two receptor complexes; the dystrophin-glycoprotein complex and integrin a7b1. To gain insight into the molecular mechanisms underlying this disorder, we performed gene expression profiling of laminin a2 chain deficient mouse limb muscle. One of the down-regulated genes encodes a protein called calcium and integrin binding protein 2 (Cib2) whose expression and function is unknown. However, the closely related Cib1 has been reported to bind integrin aIIb and may be involved in outside-in-signaling in platelets. Since Cib2 might be a novel integrin a7b1 binding protein in muscle, we have studied Cib2 expression in the developing and adult mouse. Cib2 mRNA is mainly expressed in the developing central nervous system and in developing and adult skeletal muscle. In skeletal muscle Cib2 colocalizes with integrin a7B subunit at the sarcolemma and at the neuromuscular- and myotendinous junctions. Finally, we demonstrate that Cib2 is a calcium binding protein that interacts with integrin a7Bb1D. Thus, our data suggest a role for Cib2 as a cytoplasmic effector of integrin a7Bb1D signaling in skeletal muscle Experiment Overall Design: Skeletal muscle (all hind limb skeletal muscle) from 4-weeks old laminin alpha 2 chain deficient mice and 4-weeks old wild type mice were isolated individually and RNA were extracted and hybridized on Affiymetrix microarrys. Three biological replicates from each group were analyzed.
Project description:The dataset contains 72 RNA-seq samples obtained from adult (P150) C57BL/6JCrl mice. Samples are from total heart, liver and kidney tissue. Four different genotypes are included in the data: 1) wild type, 2) transgenic Ciona intestinalis AOX in Rosa26 locus (Szibor et al. 2017, DOI: 10.1242/dmm.027839), 3) respiratory chain complex III deficient Bcs1lp.S78G knock-in mice (a GRACILE syndrome patient mutation, Leveen et al. 2011, DOI: 10.1002/hep.24031) and 4) a cross between the AOX transgenic and Bcs1lp.S78G mice (Rajendran et al. EMBO Mol Med. In press).
