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A New Enpp1 allele, Enpp1(ttw-Ham), Identified in an ICR Closed Colony

We recently have reported on a novel ankylosis gene that is closely linked to the Enpp1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) gene on chromosome 10. Here, we have discovered novel mutant mice in a Jcl:ICR closed colony with ankylosis in the toes of the forelimbs at about 3 weeks of ag...

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Autores principales: Takabayashi, Shuji, Seto, Shintaro, Katoh, Hideki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japanese Association for Laboratory Animal Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160980/
https://www.ncbi.nlm.nih.gov/pubmed/24770645
http://dx.doi.org/10.1538/expanim.63.193
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author Takabayashi, Shuji
Seto, Shintaro
Katoh, Hideki
author_facet Takabayashi, Shuji
Seto, Shintaro
Katoh, Hideki
author_sort Takabayashi, Shuji
collection PubMed
description We recently have reported on a novel ankylosis gene that is closely linked to the Enpp1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) gene on chromosome 10. Here, we have discovered novel mutant mice in a Jcl:ICR closed colony with ankylosis in the toes of the forelimbs at about 3 weeks of age. The mutant mice exhibited rigidity in almost all joints, including the vertebral column, which increased with age. These mice also showed hypogrowth with age after 16 weeks due to a loss of visceral fat, which may have been caused by poor nutrition. Histological examination and soft X-ray imaging demonstrated the ectopic ossification of various joints in the mutant mice. In particular, increased calcium deposits were observed in the joints of the toes, the carpal bones and the vertebral column. We sequenced all exons and exon/intron boundaries of Enpp1 in the normal and mutant mice, and identified a G-to-T substitution (c.259+1G>T) in the 5′ splice donor site of intron 2 in the Enpp1 gene of the mutant mice. This substitution led to the skipping of exon 2 (73 bp), which generated a stop codon at position 354 bp (amino acid 62) of the cDNA (p.V63Xfs). Nucleotide pyrophosphohydrolase (NPPH) activity of ENPP1 in the mutant mice was also decreased, suggesting that Enpp1 gene function is disrupted in this novel mutant. The mutant mice reported in this study will be a valuable animal model for future studies of human osteochondral diseases and malnutrition.
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spelling pubmed-41609802014-10-21 A New Enpp1 allele, Enpp1(ttw-Ham), Identified in an ICR Closed Colony Takabayashi, Shuji Seto, Shintaro Katoh, Hideki Exp Anim Original We recently have reported on a novel ankylosis gene that is closely linked to the Enpp1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) gene on chromosome 10. Here, we have discovered novel mutant mice in a Jcl:ICR closed colony with ankylosis in the toes of the forelimbs at about 3 weeks of age. The mutant mice exhibited rigidity in almost all joints, including the vertebral column, which increased with age. These mice also showed hypogrowth with age after 16 weeks due to a loss of visceral fat, which may have been caused by poor nutrition. Histological examination and soft X-ray imaging demonstrated the ectopic ossification of various joints in the mutant mice. In particular, increased calcium deposits were observed in the joints of the toes, the carpal bones and the vertebral column. We sequenced all exons and exon/intron boundaries of Enpp1 in the normal and mutant mice, and identified a G-to-T substitution (c.259+1G>T) in the 5′ splice donor site of intron 2 in the Enpp1 gene of the mutant mice. This substitution led to the skipping of exon 2 (73 bp), which generated a stop codon at position 354 bp (amino acid 62) of the cDNA (p.V63Xfs). Nucleotide pyrophosphohydrolase (NPPH) activity of ENPP1 in the mutant mice was also decreased, suggesting that Enpp1 gene function is disrupted in this novel mutant. The mutant mice reported in this study will be a valuable animal model for future studies of human osteochondral diseases and malnutrition. Japanese Association for Laboratory Animal Science 2014-04-26 2014 /pmc/articles/PMC4160980/ /pubmed/24770645 http://dx.doi.org/10.1538/expanim.63.193 Text en ©2014 Japanese Association for Laboratory Animal Science http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.
spellingShingle Original
Takabayashi, Shuji
Seto, Shintaro
Katoh, Hideki
A New Enpp1 allele, Enpp1(ttw-Ham), Identified in an ICR Closed Colony
title A New Enpp1 allele, Enpp1(ttw-Ham), Identified in an ICR Closed Colony
title_full A New Enpp1 allele, Enpp1(ttw-Ham), Identified in an ICR Closed Colony
title_fullStr A New Enpp1 allele, Enpp1(ttw-Ham), Identified in an ICR Closed Colony
title_full_unstemmed A New Enpp1 allele, Enpp1(ttw-Ham), Identified in an ICR Closed Colony
title_short A New Enpp1 allele, Enpp1(ttw-Ham), Identified in an ICR Closed Colony
title_sort new enpp1 allele, enpp1(ttw-ham), identified in an icr closed colony
topic Original
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160980/
https://www.ncbi.nlm.nih.gov/pubmed/24770645
http://dx.doi.org/10.1538/expanim.63.193
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