Neutral Sphingomyelinase 2 (SMPD3)-Deficiency in Mice Causes Chondrodysplasia with Unimpaired Skeletal Mineralization.

Neutral Sphingomyelinase 2 (SMPD3)-Deficiency in Mice Causes Chondrodysplasia with Unimpaired Skeletal Mineralization. Am J Pathol. 2019 Jun 11;: Authors: Stoffel W, Hammels I, Jenke B, Schmidt-Soltau I, Niehoff A Abstract SMPD3 deficiency in the neutral sphingomyelinase (Smpd3-/-) mouse results in a novel form of juvenile dwarfism, suggesting smpd3 as polygenetic determinant of body-height. SMPD3 controls homeostasis of the sphingomyelin cycle in the Golgi-compartment, essential for membrane remodeling, initiating multiform vesicle formation and transport in the Golgi secretory pathway. Using the unbiased Smpd3-/- genetic model, this study shows that the perturbed Golgi secretory pathway of chondrocytes of the epiphyseal growth zone leads to dysproteostasis, skeletal growth inhibition, malformation, and chondrodysplasia, but revealed unimpaired mineralization in primary and secondary enchondral ossification centers. This has been elaborated by biochemical analyses and immuno-histochemistry of long bones of Smpd3-/- mice. A more precise definition of the microarchitecture and three dimensional structure of the bone was asserted by peripheral quantitative computed tomography, high resolution microcomputed tomography, and less precise by dual-energy X-ray absorptiometry for osteodensitometry. Ablation of the Smpd3-locus as part of a 980 kb-deletion on chromosome 8 in the fro/fro mutant, generated by chemical mutagenesis, is held respon...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research