title: Disordered vertebral and rib morphology in pudgy mice. Structural relationships to human scoliosis.
abstract: Normal and abnormal vertebral development have been studied over the past 200 years at increasing levels of resolution as techniques for biological investigation have improved. Disordered development of the axial skeleton from the early embryonic period on leads to structurally malformed vertebrae and intervertebral discs and ribs causing the severe deformities of scoliosis, kyphosis, and kyphoscoliosis. Developmental malformation of the axial skeleton therefore has led to considerable biological and clinical interest. This work will detail our studies on the structural deformities of the vertebral column and adjacent ribs in the pudgy mouse [1] caused by mutations in the delta-like 3 (Dll3) gene of the Notch family [2]. While gene abnormalities in the pudgy mouse have been outlined, there has been no in-depth assessment of the histopathology of the pudgy vertebral and rib abnormalities that this study will provide. In addition, although congenital scoliosis has been recognized as a clinical problem since the mid-nineteenth century (1800s) [3] and accurately defined by radiography since the early twentieth century (1900s) [4-6], there have been few detailed histopathologic studies of human cases. We will also relate our histopathologic findings in the pudgy mouse to the histopathology of human vertebral and rib malformations in clinical cases of congenital scoliosis, one of which we defined in detail previously [7].
authors.affiliation: Laboratory for the Study of Skeletal Disorders, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Shapiro
mesh_terms: D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics; D000818:Animals; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology; D002417:Cattle; D002642:Chick Embryo; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007403:Intervertebral Disc / Q000196:embryology / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000502:physiology; D007714:Klippel-Feil Syndrome / Q000196:embryology / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics; D009154:Mutation; D009672:Notochord / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D010641:Phenotype; D012272:Ribs / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D012600:Scoliosis / Q000151:congenital* / Q000196:embryology / Q000235:genetics / Q000473:pathology; D013045:Species Specificity; D013131:Spine / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology
chemical_list: C511877:Dll3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins