ABSTRACT
The development and evolution of multicellular animals relies on the ability of certain cell types to synthesise an extracellular matrix (ECM) comprising very long collagen fibrils that are arranged in very ordered 3-dimensional scaffolds. Tendon is a good example of a highly ordered ECM, in which tens of millions of collagen fibrils, each hundreds of microns long, are synthesised parallel to the tendon long axis. This review highlights recent discoveries showing that the assembly of collagen fibrils in tendon is hierarchical, and involves the formation of fairly short "collagen early fibrils" that are the fusion precursors of the very long fibrils that occur in mature tendon.
Subject(s)
Fibrillar Collagens/biosynthesis , Tendons/metabolism , Animals , Extracellular Matrix/chemistry , Extracellular Matrix/metabolism , Fibrillar Collagens/metabolism , Procollagen/metabolism , Tendons/chemistryABSTRACT
Multiple epiphyseal dysplasia (MED) is a genetically heterogeneous disorder with marked clinical and radiographic variability. Traditionally, the mild "Ribbing" and severe "Fairbank" types have been used to define a broad phenotypic spectrum. Mutations in the gene encoding cartilage oligomeric-matrix protein have been shown to result in several types of MED, whereas mutations in the gene encoding the alpha2 chain of type IX collagen (COL9A2) have so far been found only in two families with the Fairbank type of MED. Type IX collagen is a heterotrimer of pro-alpha chains derived from three distinct genes-COL9A1, COL9A2, and COL9A3. In this article, we describe two families with distinctive oligo-epiphyseal forms of MED, which are heterozygous for different mutations in the COL9A2 exon 3/intron 3 splice-donor site. Both of these mutations result in the skipping of exon 3 from COL9A2 mRNA, but the position of the mutation in the splice-donor site determines the stability of the mRNA produced from the mutant COL9A2 allele.
Subject(s)
Mutation , Osteochondrodysplasias/genetics , Procollagen/genetics , Adolescent , Child , Child, Preschool , Epiphyses/diagnostic imaging , Female , Genetic Testing , Humans , Male , Osteochondrodysplasias/diagnostic imaging , Pedigree , Polymorphism, Single-Stranded Conformational , RNA Splicing , RadiographySubject(s)
Doxorubicin/adverse effects , Kidney/radiation effects , Radiation Injuries/pathology , Age Factors , Animals , Atrophy/pathology , Body Weight/drug effects , Body Weight/radiation effects , Dose-Response Relationship, Radiation , Female , Kidney/drug effects , Kidney/pathology , Kidney Glomerulus/pathology , Kidney Tubules/pathology , Mice , Organ Size/drug effects , Organ Size/radiation effectsABSTRACT
Minimal-lethal-doses (LD1/21) of Actinomycin-D (AMD), Vincristine (VCR), or Adriamycin (ADR) inhibited compensatory renal growth in unilaterally nephrectomized weanling mice. AMD transiently inhibited compensatory renal and body growth. VCR transiently inhibited kidney growth only, while ADR produced persistent kidney and body growth inhibition. 3H thymidine uptake was decreased at 5 days from controls with AMD and ADR, and increased at 14 days from controls with ADM, VCR, and ADR. Kidney DNA concentration was increased from controls at 3 days with AMD and at 8 and 14 days with ADR, but decreased from controls of 8 days with AMD and VCR. AMD and ADR inhibit compensatory renal growth and body growth in the immature mouse. VCR selectively inhibits renal growth. Renal growth inhibition with AMD, VCR, and ADR is related, in part, to a delay in the renal mitotic response to contralateral nephrectomy, and with AMD and ADR to generalized body growth supression. Chemotherapy injury to the growing mammalian kidney may be manifest as growth inhibition.
Subject(s)
Dactinomycin/pharmacology , Doxorubicin/pharmacology , Growth Inhibitors/pharmacology , Kidney/drug effects , Vincristine/pharmacology , Animals , DNA/analysis , Female , Kidney/analysis , Kidney/growth & development , Mice , Mice, Inbred Strains , Nephrectomy , Organ Size/drug effects , Time FactorsABSTRACT
Weanling mice were given 500, 1,000, 1,500, or 2,000 rads single-fraction renal irradiation immediately following unilateral nephrectomy and sacrificed 3 days or 3, 6, 12, or 24 weeks later. Inhibition of compensatory renal growth was related to both radiation dose and time following treatment; it was transient following 500 and 1,000 rads but persisted following 1,500 and 2,000 rads. Renal growth was inhibited more than body growth. These studies indicate that the weanling mouse kidney is more sensitive to radiation-induced inhibition of compensatory renal growth than adult mice or other rodents.
