A New Chondrodystrophic Mutant in Mice

Seegmiller, Robert E.; Fraser, F. Clarke; Sheldon, H.

doi:10.1083/jcb.48.3.580

Cited by 154 publications

(54 citation statements)

References 40 publications

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“…Patients with Marshall syndrome exhibit short stature and bony overgrowths on the skull (Stratton et al, 1991;Meisler et al, 1998), suggesting a role for Col11a1 in controlling bone mineralization. Further evidence for this conclusion is apparent in the Cho mice, which exhibit excess mineralization in the long bones (Seegmiller et al, 1971;Li et al, 1995). Sequence variations in the Col11a1 gene are also associated with osteoarthritis, early-onset osteoarthritis, degenerative lumbar spinal stenosis and cleft palate (Melkoniemi et al, 2003;Noponen-Hietala et al, 2003;Rodriguez et al, 2004;Jakkula et al, 2005).…”

Section: Discussionmentioning

confidence: 95%

“…In mice lacking Col11a1 (Cho mice), chondrocytes fail to fully differentiate causing a chondrodystrophic phenotype. Cho mice also have enhanced long bone mineralization, thicker trabeculae, and increased bone mass at the diaphysis (Seegmiller et al, 1971). Observations from the Cho mice suggest that Col11a1 is essential for skeletal morphogenesis because it controls type II collagen fibrillogenesis, chondrocyte maturation and bone mineralization (Seegmiller et al, 1971;Li et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Collagen 11a1 is indirectly activated by lymphocyte enhancer-binding factor 1 (Lef1) and negatively regulates osteoblast maturation

et al. 2008

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Collagen 11a1 is indirectly activated by lymphocyte enhancer-binding factor 1 (Lef1) and negatively regulates osteoblast maturation

et al. 2008

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“…The histological appearance of bm/bm epiphyseal cartilage differs considerably from that described for most other short limbed cartilage mutants including the cho/cho (28) and can~can (11) mice, nanomelic chicks (23), as well as such drug-induced micromelics as thallium-(7) or 6-aminonicotinamide-(29) treated chicks. In these other mutants, or drug-induced anomalies, chondrocytes in the epiphyseal growth zones are disordered and/or the ratio of matrix volume to cell volume is greatly reduced.…”

Section: Orkin Williams Cranley Oppke and Bi~own Cartilage Of Bramentioning

confidence: 67%

“…Unlike the brachymorphic mice, mice homozygous for chondrodysplasia (cho/cho) (28) and for the "cartilage anomaly" (can~can) (11) die at or shortly after birth. Mice homozygous for achondroplasia (cn/cn) and so-called stubby mice (stb/stb) are viable but breed poorly (12).…”

Section: Orkin Williams Cranley Oppke and Bi~own Cartilage Of Bramentioning

confidence: 99%

Defects in the cartilaginous growth plates of brachymorphic mice.

Orkin¹,

Williams²,

Cranley³

et al. 1977

The Journal of Cell Biology

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Homozygous brachymorphic (bm/bm) mice are characterized by disproportionately short stature. Newborn bm/bm epiphyseal cartilages are shorter than normal although the cells in the different zones of growth are relatively well organized. The extracellular matrix reacts poorly with stains specific for sulfated glycosaminoglycans. The ultrastructural appearance of the cartilage matrix indicates normal collagen fibrils; however, proteoglycan aggregate granules are smaller than normal and are present in reduced numbers, particularly in the columnar and hypertrophic zones of the growth plate. In addition, a prominent network of fine filaments, which are extractable in 4 M guanidine hydrochloride, are present in the bm/bm cartilage matrix. These findings suggest that a defect affecting the proteoglycan component of cartilage occurs in bm/bm mice.Numerous inherited disorders affect cartilage structure and function in man and other animals. Recently, we have studied cartilage from brachymorphic (bm/bm) mice. This mutant was first described by Lane and Dickie (12), and established by genetic studies as an autosomal recessive condition. Homozygous bm/brn mice are vigorous but have shortened long bones, shortened tails, and dome-shaped skulls. Such findings are consistent with a defect in cartilage development, and Lane and Dickie found the knee joints of 17-24 day old bin~bin mice to be shorter and thicker than normal, although chondrocytes in these epiphyseal growth plates retained good alignment (12).Cartilage is composed predominantly of one cell type, chondrocytes, surrounded by large quantities of extracellular matrix. Of the constituents of the extracellular matrix, two macromolecules, cartilage-type collagen (19, 36) and cartilage-specific proteoglycans (13,22), are synthesized by the differentiated chondrocytes. Ultrastructurally, this extracellular matrix consists of thin, 200-300 ,~ wide cartilage-type collagen fibrils and polygonal matrix granules of precipitated proteoglycan aggregates (1,6,18,25,(33)(34)(35).In examining the cartilaginous epiphyses from bm/bm mice, we have observed alterations in the morphological appearance of the epiphyseal growth plates at different stages of development, as well as differences in the extracellular matrix material which may be related to the abnormalities in tissue development found in this mutant.

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“…Type XI collagen is necessary for the successful assembly and structural integrity of fetal cartilage [26] and [3]. It is a quantitatively minor collagen which appears to regulate collagen type II fibrillogenesis in building an extensive network of thin collagen fibrils [3].…”

Section: Discussionmentioning

confidence: 99%

Expression, purification, and refolding of recombinant collagen α1(XI) amino terminal domain splice variants

Warner

Blasick

Brown

et al. 2007

Protein Expression and Purification

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The amino terminal domain of collagen type XI α1 chain is a noncollagenous structure that is essential for the regulation of fibrillogenesis in developing cartilage. The amino terminal domain is alternatively spliced at the mRNA level, resulting in proteins expressed as splice variants. These splice variants, or isoforms, have unique distribution in growing tissues, alluding to distinct roles in development. We report here a rapid and straightforward method for expression, purification and in vitro folding of recombinant collagen XI isoforms α1(XI) NTD[p7] and α1(XI) NTD[p6b+7]. The recombinant isoforms were expressed in Escherichia coli as bacterial inclusion bodies. Unfolded carboxy terminal polyhistidine tagged proteins were purified via nickel affinity chromatography and refolded with specific protocols optimized for each isoform. Purity was assessed by SDS-PAGE and correct secondary structure by a comparison of circular dichroism data with that obtained for Npp. Protein expression and purification of the recombinant collagen XI splice variants will allow further studies to elucidate the structure and molecular interactions with components of the extracellular matrix. This research will clarify the mechanism of collagen XI mediated regulation of collagen fibrillogenesis.

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A New Chondrodystrophic Mutant in Mice

Cited by 154 publications

References 40 publications

Collagen 11a1 is indirectly activated by lymphocyte enhancer-binding factor 1 (Lef1) and negatively regulates osteoblast maturation

Collagen 11a1 is indirectly activated by lymphocyte enhancer-binding factor 1 (Lef1) and negatively regulates osteoblast maturation

Defects in the cartilaginous growth plates of brachymorphic mice.

Expression, purification, and refolding of recombinant collagen α1(XI) amino terminal domain splice variants

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