Biomedical subjects

M Paulsson

Publications and source records attributed to M Paulsson.

At least 55 records · Page 3Linked to original sources

PubMed1999

Follicle-forming cat thyroid cell lines synthesizing extracellular matrix and basal membrane components: a new tool for the study of thyroidal morphogenesis.

Interactions between follicular epithelial cells and extracellular matrix (ECM) are supposed to play an important role in the development and maintenance of thyroid tissue architecture. In the present study we have therefore investigated the synthesis of ECM components by a feline thyroid cell line which is able to form follicle-like structures in vitro, and also in v-ras-transfected and control-transfected sublines. Transfections were performed by lipofection with pZSR (viral Harvey ras gene; neo) and pSV2-neo (control, neo only) plasmids. We have adapted a semisolid culture system composed exclusively of polymerized alginate and therefore devoid of ECM components. Feline cells embedded in alginate gels as single cells and cultured for up to 90 days formed cell clusters within 10 days. Follicle-like structures were formed in the original cell lines and also in the v-ras- and control-transfected cells. Differences in proliferation rates were observed, the v-ras-transfected cells growing up to two to three times faster than the non-transfected cells. Immunostaining was done using rabbit first antibodies directed against mouse collagen IV, human fibronectin, laminin (tumor Engelbreth-Holm-Swarm laminin), perlecan and other ECM components. For comparison, immunostaining was also performed on cryosections of nodular goiters of six hyperthyroid cats. The cell lines and their transfected clones stained strongly positive for collagen IV and fibronectin, and positively but less strongly for laminin and perlecan. The cat goiter tissue stained positively for collagen IV, laminin, perlecan, and fibronectin, and positive staining for S-laminin (containing the beta2-chain) was seen in blood vessel walls in this tissue. In conclusion, cat cell lines grow three-dimensionally in alginate beads over several weeks, they form follicle-like structures and express the same ECM components as the native cat goiter tissue. Transfection with v-ras does increase proliferation rate, but does not fundamentally alter formation of follicle-like structures and ECM expression. Alginate gel culture is a promising new tool for the study of follicular morphogenesis, polarity, the expression pattern of ECM components and of the interaction between thyrocytes and ECM. It avoids interference caused by gels composed of ECM components.

Alginates↗

PubMed1999

Recombinant human tissue transglutaminase ELISA for the diagnosis of gluten-sensitive enteropathy.

BACKGROUND: Tissue transglutaminase (TGc) has recently been identified as the major, if not the sole, autoantigen of gluten-sensitive enteropathy (GSE). We developed and validated an ELISA based on the human recombinant antigen and compared it to existing serological tests for GSE [guinea pig TGc ELISA and endomysium antibody (EMA) test]. METHODS: Human TGc was expressed in the human embryonic kidney cell line 293-EBNA as a C-terminal fusion protein with the eight-amino acid Strep-tag II allowing one-step purification via streptavidin affinity chromatography. We carried out ELISA assays for IgA antibodies against TGc using calcium-activated human and guinea pig TGc. The sera were also tested on monkey esophagus sections by indirect immunofluorescence for IgA EMA. We examined 71 serum samples from patients with GSE (38 with celiac disease, 33 with dermatitis herpetiformis), including 16 on therapy, and 53 controls. RESULTS: The human TGc could be expressed and purified as an active enzyme giving a single band on a Coomassie-stained gel. The mean intra- and interassay CVs for the human TGc ELISA were 3.2% and 9.2%, respectively. The area under the ROC curve was 0.999. The specificity and sensitivity were 98.1% (95% confidence interval, 95.7-100%) and 98.2% (95.9-100%), respectively. CONCLUSIONS: The human TGc ELISA was somewhat superior to the guinea pig TGc ELISA, and was as specific and sensitive as the EMA test. The human TGc-based ELISA is the method of choice for easy and noninvasive screening and diagnosis of GSE.

Adolescent↗

PubMed1998

Genomic organisation, alternative splicing and primary structure of human matrilin-4.

We have recently cloned a cDNA for mouse matrilin-4. By sequence comparison we identified the 12 kb long human matrilin-4 gene as a part of a high-throughput genomic sequence (HS453C12) in the databases. Additionally we found a human matrilin-4 expressed sequence tag (H54037) in the database that had been mapped to chromosome 20q13.1-2. The gene contains 10 exons and, like the matrilin-1 gene, the human matrilin-4 gene contains an AT-AC intron between the two exons encoding the coiled-coil domain. The cDNA sequence of human matrilin-4 was determined by sequencing of RT-PCR products obtained from mRNA of the human embryonic kidney cell line HEK 293. At the amino acid level it showed an overall sequence identity to the mature mouse matrilin-4 of 91% with a maximum of 97% in the second vWFA-like module. Alternative splicing leads to three different mRNAs. They all encode the putative signal peptide, the two vWFA-like domains and the potential coiled-coil alpha-helical oligomerisation domain but differ in that either one, two or three EGF-like domains are retained in the mature mRNA. Due to a G to A mutation at the splice donor site of intron C, the third exon encodes an untranslated pseudo-exon specifying the first EGF-like domain when compared to mouse matrilin-4.

Alternative Splicing↗

PubMed1998

The targeted deletion of the LAMC1 gene.

Laminin is required for the production of a basement membrane in both the early embryo and in the embryoid body. The absence of the gamma 1 chain leads to different processing of the other subunits in the trimer and prevents the production of a polymerizing laminin molecule. Collagen IV and perlecan are not able to compensate for the loss of the laminin molecule, and nidogen, which would normally bind to the gamma 1 chain, is almost completely lost from the embryoid body. In the embryo the failure of the basement membrane results in embryonic lethality at embryonic day 5.5, a time when the primitive endoderm is differentiating to visceral and parietal endoderm, and the latter is migrating out of the inner cell mass over the trophectoderm. It is likely that failure in one or both of these events leads to the death of the embryo. The absence of the trophectodermal basement membrane normally present in the blastocyst appears not to be necessary for the formation of the blastocystic cavity, which depends on the formation of a polarized epithelium. Hence the first epithelium produced in the developing embryo does so independently of a basement membrane.

Animals↗

PubMed1998

Matrilin-4, a new member of the matrilin family of extracellular matrix proteins.

Mouse cDNA encoding for matrilin-4 was cloned and the primary structure of this fourth member of the matrilin family was deduced from the nucleotide sequence. The protein precursor of 624 amino acids consists of a putative signal peptide, two vWFA-like domains linked by four epidermal growth factor-like modules and a potential coiled-coil alpha-helical oligomerization domain at the C-terminus. The predicted Mr of the mature protein is 66 442. Expression in lung, brain, sternum, kidney and heart was detected by Northern blot analysis of mouse mRNA. Additionally an alternatively spliced mRNA lacking the sequence coding for the first vWFA domain was found in 7 weeks old mice leading to a protein precursor of 434 amino acids and a predicted Mr of the mature protein of 45468.

Alternative Splicing↗

PubMed1998

PACSIN, a brain protein that is upregulated upon differentiation into neuronal cells.

To identify genes that are differentially expressed during self-repair processes in mouse brain, we screened a subtracted cDNA library enriched for brain-specific clones. One of these clones, H74, detected a 4.4-kb mRNA predominantly expressed in brain and dorsal root ganglia neurons. Expression increased continuously during the lifespan and the state of differentiation, but decreased after entorhinal-cortex lesion. A full-length cDNA clone was isolated from a cerebellum cDNA library and characterized. Sequence analysis and database search revealed high sequence similarity to FAP52, a protein expressed in focal-adhesion contacts, and uncharacterized Echinococcus and Caenorhabditis elegans gene products. Furthermore, peptide sequences derived from human cDNA fragments showed up to 65% sequence identity at the amino acid level. The presence of a C-terminal src homology 3 (SH3) domain and its phosphorylation by casein kinase 2 (CK2) and protein kinase C (PKC) imply a role in signaling. Here we demonstrate that the gene encodes a phosphoprotein, referred to as PACSIN, with a restricted spatial and temporal expression pattern.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Immunohistochemical distribution of type VI collagen in normal and glaucomatous human trabecular meshwork.

BACKGROUND: An abnormally increased presence of type VI collagen has been shown in the lamina cribrosa of patients with primary and secondary glaucoma. This study was undertaken to investigate the pattern of type VI collagen within the aqueous outflow structures of glaucoma patients. METHODS: Trabecular meshwork samples of eight normal donor eyes and trabeculectomy specimens of 21 patients with different types of glaucoma were processed for either cryo-sectioning or for paraffin embedding. Immunohistochemical staining was conducted by use of polyclonal rabbit antibodies against human collagen type VI. RESULTS: Immunoreactivity for type VI collagen was evident in the cores of all trabecular beams. The strongest staining was detected in the uveal region of the human trabecular meshwork. Immunohistochemical labelling for type VI collagen was not more pronounced in the aqueous outflow structures of glaucoma patients than in normal eyes. CONCLUSION: Collagen type VI is a ubiquitous structural component of the extracellular matrix in the human trabecular meshwork. However, type VI collagen does not appear to be of greater importance for the increased trabecular outflow resistance in glaucoma patients than in normal eyes.

Adolescent↗

PubMed1998

Interactions between endothelium-derived relaxing factors in the rat hepatic artery: focus on regulation of EDHF.

1. In rat isolated hepatic arteries contracted with phenylephrine, acetylcholine and the calcium ionophore A23187 each elicit endothelium-dependent relaxations, which involve both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). However, the contribution of prostanoids to these responses, and the potential interaction between EDHF and other endothelium-derived relaxing factors have not been examined. 2. In the presence of the NO synthase inhibitor N(G)-nitro-L-arginine (L-NOARG, 0.3 mM) and a mixture of charybdotoxin (0.3 microM) and apamin (0.3 microM), inhibitors of the target potassium (K) channel(s) for EDHF, acetylcholine and A23187 each induced a concentration-dependent and almost complete relaxation, which was abolished in the additional presence of indomethacin (10 microM). Thus, in addition to EDHF and NO, a relaxing factor(s) generated by cyclo-oxygenase (COX) contributes to endothelium-dependent relaxation in the rat hepatic artery. 3. The resting membrane potentials of endothelium-intact and endothelium-denuded vascular segments were -57 mV and -52 mV, respectively (P>0.05). In intact arteries, the resting membrane potential was not affected by L-NOARG plus indomethacin, but reduced to -47 mV in the presence of charybdotoxin plus apamin. Acetylcholine and A23187 (10 microM each) elicited a hyperpolarization of 13 mV and 15 mV, respectively. The hyperpolarization induced by these agents was not affected by L-NOARG plus indomethacin (12 mV and 14 mV, respectively), but reduced in the presence of charybdotoxin plus apamin (7 mV and 10 mV, respectively), and abolished in the combined presence of charybdotoxin, apamin and indomethacin. 4. The NO donor 3-morpholino-sydnonimine (SIN-1) induced a concentration-dependent relaxation, which was unaffected by charybdotoxin plus apamin, but abolished by the selective soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 microM). SIN-1 (10 microM) did not alter the resting membrane potential in endothelium-denuded vascular segments. 5. The COX-dependent relaxation induced by acetylcholine was abolished following exposure to 30 mM KCl, but unaffected by glibenclamide (10 microM). The prostacyclin analogue iloprost induced a concentration-dependent relaxation, which was also abolished in 30 mM KCl and unaffected by the combined treatment with glibenclamide, charybdotoxin and apamin. Iloprost (10 microM) induced a glibenclamide-resistant hyperpolarization (8 mV with and 9 mV without glibenclamide) in endothelium-denuded vascular segments. 6. Exposure to SIN-1 or iloprost did not affect the EDHF-mediated relaxation induced by acetylcholine (i.e. in the presence of L-NOARG and indomethacin). Replacement of L-NOARG with the NO scavenger oxyhaemoglobin (10 microM) or the soluble guanylate cyclase inhibitor ODQ (10 microM) or methylene blue (10 microM), which all significantly inhibited responses to endothelium-derived NO, did not affect the acetylcholine-induced relaxation in the presence of indomethacin, indicating that endogenous NO also does not suppress EDHF-mediated responses. 7. These results show that, in addition to EDHF and NO, an endothelium-derived hyperpolarizing factor(s) generated by COX contributes significantly to endothelium-dependent relaxation in the rat heptic artery. Neither this factor nor NO seems to regulate EDHF-mediated responses. Thus, EDHF does not serve simply as a 'back-up' system for NO and prostacyclin in this artery. However, whether EDHF modulates the NO and COX pathways remains to be determined.

Animals↗

PubMed1998

Alginate gel culture allows the retention of extracellular matrix and follicular structure of rat thyroid tissue but does not lead to the formation of follicles by FRTL-5 cells.

Extracellular matrix (ECM) and basement membrane (BM) components were studied by immunohistological methods in native rat thyroid tissue, and in rat thyroid tissue and FRTL-5 cells cultured in a three-dimensional alginate bead system. In all three situations, the presence of collagen IV, laminin, perlecan, and fibronectin was demonstrated. There were marked differences between rat thyroid tissue and FRTL-5 cells in culture. Rat thyroid tissue maintained a follicular structure, whereas FRTL-5 cells did not form follicles. Rat thyroid cells multiplied more slowly than FRTL-5 cells and thyroglobulin (Tg) was visible in the follicular lumen, while in FRTL-5 cells Tg was only seen intracellularly. Tg iodination was much lower in FRTL-5 cells than in rat cells. In rat thyroid cells, positive staining for collagen IV, laminin, and perlecan was seen in thin membranes around individual follicles, and for fibronectin around groups of follicles. In FRTL-5 cells, these ECM/BM components could be identified, but were not organized into equally regular networks around groups of cells. These results demonstrate that of the two types of cells examined, primary cultures of rat thyroid cells in alginate beads maintain structural and functional similarities to native thyroid tissue and would therefore be suitable for future in vitro studies of thyroidal ECM/BM and their interrelationship with growth and function of this organ. FRTL-5 cells cultured in alginate beads show some functional, but not structural similarities to native thyroid tissue and so would be less valuable for use in such studies.

Alginates↗

PubMed1998

Laminin heterogeneity around Schlemm's canal in normal humans and glaucoma patients.

BACKGROUND: The laminins play an important role in cell attachment to the extracellular matrix. This study was undertaken in order to investigate and to compare the presence of several laminin chains and isoforms in normal and glaucomatous trabecular meshwork. METHODS: Fresh-frozen trabeculectomy specimens from glaucoma patients and trabecular meshwork from human donor eyes were included for immunohistochemistry. We used antibodies against laminin 1 (EHS-laminin/alpha1beta1gamma1), laminin 2 (merosin/alpha2,beta1gamma1), the subunits of alpha2 (M laminin), beta1 B1laminin), gamma1 (beta2laminin) and beta2 (s laminin) and gamma2 and the associated glycoprotein nidogen. RESULTS: For laminin 1, laminin 2, the subunits alpha2;, beta1, beta2, gamma1 and nidogen, the immunoreactivity of the juxtacanalicular zone underneath the inner wall of Schlemm's canal was always stronger than of the uveal and corneoscleral trabecular meshwork. Staining for laminin chain gamma2 could not be demonstrated in the outflow structures. Pattern and intensity of labelling for the laminins were not different between normal and glaucomatous eyes. DISCUSSION: Heterogeneity of the laminins suggests structural complexity of the juxtacanalicular region. However, the presence of laminin around Schlemm's canal seems to be unaffected by glaucoma and by age. This might indicate maintenance of basement membrane stability in the trabecular meshwork for life.

Adult↗

PubMed1997

Primary structure of matrilin-3, a new member of a family of extracellular matrix proteins related to cartilage matrix protein (matrilin-1) and von Willebrand factor.

A mouse cDNA encoding for matrilin-3, the third member of the novel matrilin family of extracellular matrix proteins, was cloned. The protein precursor of 481 amino acids consists of a putative signal peptide, a short positively charged sequence, a single vWFA-like domain followed by four epidermal growth factor-like modules and a potential coiled-coil alpha-helical oligomerization domain at the C-terminus. It is the smallest member of the matrilin family with a predicted Mr of the mature protein of 48 902. The primary structure of a C-terminal portion of 310 amino acids of the human matrilin-3 was determined and showed a sequence identity to the mouse matrilin-3 of 84.8%. Northern blot hybridization of mouse matrilin-3 mRNA showed a 2.9 kb mRNA expressed in sternum, femur and trachea and indicates a cartilage-specific expression.

Amino Acid Sequence↗

PubMed1997

Primary structure and expression of matrilin-2, the closest relative of cartilage matrix protein within the von Willebrand factor type A-like module superfamily.

A mouse cDNA encoding a novel member of the von Willebrand factor type A-like module superfamily was cloned. The protein precursor of 956 amino acids consists of a putative signal peptide, two von Willebrand factor type A-like domains connected by 10 epidermal growth factor-like modules, a potential oligomerization domain, and a unique segment, and it contains potential N-glycosylation sites. A sequence similarity search indicated the closest relation to the trimeric cartilage matrix protein (CMP). Since they constitute a novel protein family, we introduce the term matrilin-2 for the new protein, reserving matrilin-1 as an alternative name for CMP. A 3. 9-kilobase matrilin-2 mRNA was detected in a variety of mouse organs, including calvaria, uterus, heart, and brain, as well as fibroblast and osteoblast cell lines. Expressed human and rat cDNA sequence tags indicate a high degree of interspecies conservation. A group of 120-150-kDa bands was, after reduction, recognized specifically with an antiserum against the matrilin-2-glutathione S-transferase fusion protein in media of the matrilin-2-expressing cell lines. Assuming glycosylation, this agrees well with the predicted minimum Mr of the mature protein (104,300). Immunolocalization of matrilin-2 in developing skeletal elements showed reactivity in the perichondrium and the osteoblast layer of trabecular bone. CMP binds both collagen fibrils and aggrecan, and because of the similar structure and complementary expression pattern, matrilin-2 is likely to perform similar functions in the extracellular matrix assembly of other tissues.

Amino Acid Sequence↗

PubMed1997

[Variability of laminin isoforms in the limbus region of the eye].

BACKGROUND: Cell adhesion in the limbal region is of outstanding importance for the regeneration of the corneal epithelium and for repair mechanisms after antiglaucomatous fistulating surgery. In the basement membranes cell adhesion is largely modified by the extracellular matrix protein laminin. The aim of our study was to establish the immunohistochemical pattern of the different laminin-isoforms and subunits in the basal membrane of the limbal conjunctiva and episcleral vessels. MATERIAL AND METHOD: For immunohistochemistry five normal human donor eyes were included; we used antibodies against the laminin heterotrimers 1 and 2, against the laminin subunits alpha 2, beta 1, beta 2, gamma 1, gamma 2 and against the laminin-associated protein nidogen. RESULTS: The basement membrane of the limbal conjunctiva reveals immunoreactivity against all used antibodies. The subconjunctival and episcleral vessels showed no staining for the laminin subunit gamma 2, but for all other used antibodies. CONCLUSION: The basement membrane of the limbal and conjunctival epithelium as well as the basement membrane of subconjunctival and episcleral vessels express a broad spectrum of laminin variants. This diversity emphasizes functional specialization of the limbal region, although the exact importance of the laminin variants is still unknown.

Adult↗

PubMed1997

Expression patterns of extracellular matrix components in native and cultured normal human thyroid tissue and in human toxic adenoma tissue.

The extracellular matrix (ECM) and basement membranes (BM, a specialized form of ECM) greatly influence proliferation, differentiation, and function of cells and the structure of tissues. While a considerable amount of information is available on thyroid cellular proliferation, differentiation and function, much less is known about thyroid ECM and BM. In this study the presence of the ECM/BM components fibronectin, collagen IV, alpha1, beta1, gamma1 laminin, several laminin variants, osteonectin, and perlecan was demonstrated in cryosections of nonadenomatous and toxic adenoma human thyroid tissue. Also, positive immunohistochemical staining for collagen IV, laminin, perlecan, and fibronectin was obtained in sections of human thyroid tissue cultured in a three-dimensional (alginate) culture system. The present study provides methods and data that will facilitate the investigation of the interaction between cells and ECM in thyroid tissue.

Adenoma↗

PubMed1997

Small fragments of cartilage oligomeric matrix protein in synovial fluid and serum as markers for cartilage degradation.

We determined the tissue distribution of cartilage oligomeric matrix protein (COMP) in man and evaluated COMP in synovial fluid (SF) and serum. COMP was purified from human articular cartilage. Polyclonal antibodies were used to detect COMP in tissue cryosections and protein extracts. COMP was determined quantitatively and qualitatively in SF and serum by competitive enzyme-linked immunosorbent assay and immunoblotting. Knee joint SF was taken from nine cadaveric and six living controls, 52 patients with osteoarthritis (OA), 85 patients with rheumatoid arthritis (RA) and 60 patients with other forms of inflammatory arthritis. The degradative potential of SF on native COMP was tested in vitro. The highest concentrations of COMP were measured in articular cartilage and meniscus, the lowest in rib and trachea. Compared with controls, the concentrations of COMP in SF and serum were elevated in 36 and 50% of the patients. A total of 84% of patients with RA and 60% of patients with other forms of inflammatory arthritis showed significant amounts of low-molecular-weight COMP fragments (50-70 kDa) in SF. In contrast, SF fragments were present in only 21% of the OA patients. Furthermore, 13% of SF taken from patients with RA or other forms of inflammatory arthritis were able to degrade COMP in vitro. Using inhibitors, the involvement of serine proteinases could be demonstrated in only 8% of the cases. Based on these results, the absolute levels of COMP in SF and serum, and its fragmentation pattern in SF, seem to be promising as markers of joint tissue metabolism.

Adult↗

PubMed1997

Protein cross-linking mediated by tissue transglutaminase correlates with the maturation of extracellular matrices during lung development.

At birth, the mammalian lung is still immature. The alveoli are not yet formed and the interairspace walls contain two capillary layers which are separated by an interstitial core. After alveolarization (first 2 postnatal weeks in rats) the alveolar septa mature: their capillary layers merge, the amount of connective tissue decreases, and the mature lung parenchyma is formed (second and third week). During the first 3 wk of life the role of tissue transglutaminase (tTG) was studied in rat lung by immunostaining of cryostat and paraffin sections, by Northern and Western blotting, and by a quantitative determination of gamma-glutamyl-epsilon-lysine. While enzyme activity and intracellular tTG were already present before term, the enzyme product (gamma-glutamyl-epsilon-lysine-crosslink) and extracellular tTG appeared between postnatal days 10 and 19 in the lung parenchyma. In large blood vessels and large airways, which mature earlier than the parenchyma, both the enzyme product and extracellular tTG had already appeared at the end of the first postnatal week. We conclude that tTG is expressed and externalized into the extracellular matrix of lung shortly before maturation of an organ area. Because tTG covalently and irreversibly crosslinks extracellular matrix proteins, we hypothesize that it may prevent or delay further remodeling of basement membranes and may stabilize other extracellular components, such as microfibrils.

Animals↗

PubMed1996

Interaction of cartilage matrix protein with aggrecan. Increased covalent cross-linking with tissue maturation.

Cartilage matrix protein (CMP) is a trimeric protein present in many types of cartilage extracellular matrix. It has recently been purified under native conditions that allowed the proposal of a structural model (Hauser, N., and Paulsson, M. (1994) J. Biol. Chem. 269, 25747-25753). To examine the functional properties of CMP we studied its interaction with aggrecan within cartilage extracellular matrix. Aggrecan-enriched fractions were purified from bovine tracheal cartilage of different ages under nondenaturing and denaturing conditions, respectively, and characterized by a combination of biochemical methods and electron microscopy. The fractions contained a pool of CMP noncovalently associated with aggrecan as well as a pool of CMP that appears covalently cross-linked to the aggrecan core protein. Only about two thirds of the CMP subunits could be released even upon reduction under denaturing conditions. It appears that CMP is attached by a nonreducible covalent interaction of one of its subunits with the protein core. The amount of CMP strongly bound to aggrecan increases with age. Electron microscopy revealed interaction sites for CMP in the extended chondroitin-sulfate attachment domain E2. In old tissue five distinct binding sites for CMP were found while in young cartilage only three of these were occupied. The extent of decoration of E2 with CMP increases with age.

Aggrecans↗

PubMed1996

Cloning, sequencing and expression analysis of mouse cartilage matrix protein cDNA.

A cDNA encoding the mouse cartilage matrix protein (CMP) was cloned following the reverse-transcription polymerase chain reaction and rapid amplification of cDNA ends procedures using mRNA isolated from trachea. The open reading frame encodes a product of 500 amino acids. Large parts of the protein have been completely conserved when compared to chicken and human sequences, including all 12 cysteine residues of the mature CMP. In situ hybridization reveals an even distribution of the CMP mRNA in the developing skeleton, which is followed by a zonal distribution paralleling hypertrophy and calcification. From early cartilage differentiation and onwards, CMP transcript is absent in the forming articular surfaces and intervertebral discs. Extraskeletal expression of CMP mRNA was detected in the adult eye.

Amino Acid Sequence↗