Disease relevance of Col11a2

• Col11a1 and Col11a2 mRNA expression in the developing mouse cochlea: implications for the correlation of hearing loss phenotype with mutant type XI collagen genotype [1].
• We found that Col11a2 promoter activity was inhibited by transfection of the NT2 expression vector in RSC cells, a chondrosarcoma cell line [2].
• OBJECTIVE: To investigate the incidence and severity of osteoarthritis (OA) and the effects of voluntary wheel running in normal mice and mice carrying either a targeted inactivation of one allele, heterozygous 'knockout', of Col2a1 gene or both alleles, homozygous 'knockout', of Col11a2 gene [3].

High impact information on Col11a2

• Sox9 binds to essential sequences in the Col2a1 and collagen alpha2(XI) gene (Col11a2) chondrocyte-specific enhancers and can activate these enhancers in non-chondrocytic cells [4].
• Mice with a targeted disruption of Col11a2 also were shown to have hearing loss [5].
• Here, we demonstrate that NT2 functions as a negative regulator of Col11a2 [2].
• In situ hybridization analysis of developing mouse cartilage showed that NT2 mRNA is highly expressed by hypertrophic chondrocytes but is minimally expressed by resting and proliferating chondrocytes, in an inverse correlation with the expression patterns of Col11a2 [2].
• We investigated a tissue-specific transcriptional enhancer in the first intron of the alpha2(XI) collagen gene (Col11a2) [6].

Biological context of Col11a2

• The present study has identified two short chondrocyte-specific enhancer elements within a region in the 5' portion of the type XI collagen gene Col11a2 that has previously been shown to influence chondrocyte-specific expression in transgenic mice [7].
• The Col11a2 elements directed gene expression in transient transfections of chondrocytes but not fibroblasts, and their activity was abolished by mutation of the HMG-like sites [7].
• Finally, the Col11a2 enhancer elements both directed transgene expression to cartilage in developing mouse embryos [7].
• These Col11a2 enhancer elements, like the Col2a1 enhancer, contain several sites with homology to the high mobility group (HMG) protein-binding consensus sequence [7].
• Transient transfection assays using reporter gene constructs revealed that a 60-base pair (bp) segment within intron 1 increased promoter activity of Col11a2 in rat chondrosarcoma cells but not in either BalB/3T3 cells or undifferentiated ATDC5 cells, suggesting that it contained cell type-specific enhancer activity [6].

Anatomical context of Col11a2

• The greater epithelial ridge appeared to be the main, if not only, source of mRNA encoding Col11a1 and Col11a2 in the tectorial membrane [1].
• RESULTS: Similar, diffuse expression of Col11a1 and Col11a2 mRNA was first observed in the cochlear duct at embryonic Day 15.5, with increasingly focal hybridization being noted at postnatal Days 1 and 5 in the greater epithelial ridge and lateral wall of the cochlea [1].
• To identify a protein factor that bound to the 24-bp sequence of the Col11a2 promoter, we screened a mouse limb bud cDNA expression library in the yeast one-hybrid screening system and obtained the cDNA clone NT2 [2].
• A 1,064 bp fragment from the promoter region of the Col11a2 gene drives lacZ expression not only in cartilage but also in osteoblasts adjacent to regions undergoing both endochondral and intramembranous ossification in mouse embryos [8].

Associations of Col11a2 with chemical compounds

• However, translation of the full-length Col11a2 chain was unable to occur because of the presence of premature termination codons within the inverted neomycin-resistant gene [9].

Physical interactions of Col11a2

• Gel shift assays showed that NT2 bound a specific sequence within the 24-bp site of the Col11a2 promoter [2].

Regulatory relationships of Col11a2

• The expression vector for mutant NT2 lacking the KRAB domain failed to inhibit Col11a2 promoter activity [2].

Other interactions of Col11a2

• The previously defined Ke5 probe could be shown to map into the large Col11a2 gene [10].
• At postnatal Day 13, Col11a1 and Col11a2 expression became more focal and co-localized in the inner sulcus, Claudius' cells and cells of Boettcher [1].
• Chondrocyte-specific enhancer elements in the Col11a2 gene resemble the Col2a1 tissue-specific enhancer [7].
• These results suggest that the 7-bp sequence within intron 1 plays a critical role in the cartilage-specific enhancer activity of Col11a2 through Sox9-mediated transcriptional activation [6].

Analytical, diagnostic and therapeutic context of Col11a2

• In electrophoretic mobility shift assays, the Col11a2 elements formed a DNA-protein complex that was dependent on the presence of the HMG-like sites [7].
• Transgenic mice were prepared by homologous recombination with a Col11a2 targeting gene in which an inverted neomycin-resistant gene was inserted between restriction sites in exons 27 and 28 [9].

References