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3 Rescue of TTD-Associated Segmental Progeroid Features in Compound Heterozygous Xpd TTD/†XPCS Mice\n(A) Photographs of 20-mo-old wt, compound heterozygous XpdTTD/†XPCS, and homozygous XpdTTD/TTD mice. Note the extreme cachexia (lack of subcutaneous fat) in the XpdTTD/TTD mouse and the absence of this phenotype in wt and XpdTTD/†XPCS mice.\n(B) Radiographs of 20-mo-old male wt, XpdTTD/†XPCS, and XpdTTD/TTD mice. Ageing XpdTTD/TTD mice develop kyphosis (curvature of the spinal column) and reduction of bone mineral density as shown in the 6–8 segment of the tail vertebrae counted from the pelvis (see close-up at right). Note the absence of these features in the XpdTTD / † XPCS mouse.\n(C) Quantification of relative bone mineral density of tail vertebrae from 20-mo-old male wt (n = 3), XpdTTD/†XPCS (n = 4), and XpdTTD/TTD (n = 3) mice. The p-values indicate the significance of the difference relative to XpdTTD/TTD. Error bars indicate SEM.\n(D) Body weight curves as a function of time. Note that the age-dependent cachexia observed in XpdTTD/TTD mice was rescued in both male and female XpdTTD / †XPCS mice. Significant differences between wt and XpdTTD/TTD but not between wt and XpdTTD/†XPCS mice were observed at 9 and 18 mo of age as indicated by asterisks. Error bars indicate SEM.\nTable 2 Pleiotropic Xpd Biallelic Effects in Mice and Cells To determine whether the homozygous lethal Xpd†XPCS allele was unique in its ability to ameliorate symptoms associated with the XpdTTD allele, we generated compound heterozygous XpdTTD/†XP mice by crossing the corresponding heterozygous animals."}

{"project":"craft-ca-core-dev","denotations":[{"id":"T7952","span":{"begin":90,"end":93},"obj":"PR:000007164"},{"id":"T7953","span":{"begin":104,"end":108},"obj":"NCBITaxon:10088"},{"id":"T7954","span":{"begin":164,"end":167},"obj":"PR:000007164"},{"id":"T7955","span":{"begin":193,"end":196},"obj":"PR:000007164"},{"id":"T7956","span":{"begin":204,"end":208},"obj":"NCBITaxon:10088"},{"id":"T7957","span":{"begin":245,"end":261},"obj":"UBERON:0002190"},{"id":"T7958","span":{"begin":270,"end":273},"obj":"PR:000007164"},{"id":"T7959","span":{"begin":281,"end":286},"obj":"NCBITaxon:10088"},{"id":"T7960","span":{"begin":331,"end":334},"obj":"PR:000007164"},{"id":"T7961","span":{"begin":344,"end":348},"obj":"NCBITaxon:10088"},{"id":"T7962","span":{"begin":388,"end":391},"obj":"PR:000007164"},{"id":"T7963","span":{"begin":406,"end":409},"obj":"PR:000007164"},{"id":"T7964","span":{"begin":417,"end":421},"obj":"NCBITaxon:10088"},{"id":"T7965","span":{"begin":423,"end":429},"obj":"GO:0007568"},{"id":"T7966","span":{"begin":430,"end":433},"obj":"PR:000007164"},{"id":"T7967","span":{"begin":441,"end":445},"obj":"NCBITaxon:10088"},{"id":"T7968","span":{"begin":481,"end":494},"obj":"UBERON:0001130"},{"id":"T7969","span":{"begin":518,"end":525},"obj":"CHEBI:46662"},{"id":"T7970","span":{"begin":569,"end":573},"obj":"UBERON:0002415"},{"id":"T7971","span":{"begin":574,"end":583},"obj":"UBERON:0002412"},{"id":"T7972","span":{"begin":601,"end":607},"obj":"UBERON:0002355"},{"id":"T7973","span":{"begin":675,"end":678},"obj":"PR:000007164"},{"id":"T7974","span":{"begin":691,"end":696},"obj":"NCBITaxon:10088"},{"id":"T7975","span":{"begin":734,"end":741},"obj":"CHEBI:46662"},{"id":"T7976","span":{"begin":753,"end":757},"obj":"UBERON:0002415"},{"id":"T7977","span":{"begin":758,"end":767},"obj":"UBERON:0002412"},{"id":"T7978","span":{"begin":800,"end":803},"obj":"PR:000007164"},{"id":"T7979","span":{"begin":826,"end":829},"obj":"PR:000007164"},{"id":"T7980","span":{"begin":845,"end":849},"obj":"NCBITaxon:10088"},{"id":"T7981","span":{"begin":920,"end":923},"obj":"PR:000007164"},{"id":"T7982","span":{"begin":1052,"end":1055},"obj":"PR:000007164"},{"id":"T7983","span":{"begin":1063,"end":1067},"obj":"NCBITaxon:10088"},{"id":"T7984","span":{"begin":1104,"end":1107},"obj":"PR:000007164"},{"id":"T7985","span":{"begin":1119,"end":1123},"obj":"NCBITaxon:10088"},{"id":"T7986","span":{"begin":1164,"end":1167},"obj":"PR:000007164"},{"id":"T7987","span":{"begin":1198,"end":1201},"obj":"PR:000007164"},{"id":"T7988","span":{"begin":1211,"end":1215},"obj":"NCBITaxon:10088"},{"id":"T9234","span":{"begin":1325,"end":1328},"obj":"PR:000007164"},{"id":"T9235","span":{"begin":1331,"end":1338},"obj":"SO:0001023"},{"id":"T9236","span":{"begin":1350,"end":1354},"obj":"NCBITaxon:10088"},{"id":"T2501","span":{"begin":1408,"end":1411},"obj":"PR:000007164"},{"id":"T2502","span":{"begin":1417,"end":1423},"obj":"SO:0001023"},{"id":"T2503","span":{"begin":1493,"end":1496},"obj":"PR:000007164"},{"id":"T2504","span":{"begin":1500,"end":1506},"obj":"SO:0001023"},{"id":"T2505","span":{"begin":1543,"end":1546},"obj":"PR:000007164"},{"id":"T2506","span":{"begin":1554,"end":1558},"obj":"NCBITaxon:10088"},{"id":"T2507","span":{"begin":1602,"end":1609},"obj":"NCBITaxon:33208"}],"text":"\nFigure 3 Rescue of TTD-Associated Segmental Progeroid Features in Compound Heterozygous Xpd TTD/†XPCS Mice\n(A) Photographs of 20-mo-old wt, compound heterozygous XpdTTD/†XPCS, and homozygous XpdTTD/TTD mice. Note the extreme cachexia (lack of subcutaneous fat) in the XpdTTD/TTD mouse and the absence of this phenotype in wt and XpdTTD/†XPCS mice.\n(B) Radiographs of 20-mo-old male wt, XpdTTD/†XPCS, and XpdTTD/TTD mice. Ageing XpdTTD/TTD mice develop kyphosis (curvature of the spinal column) and reduction of bone mineral density as shown in the 6–8 segment of the tail vertebrae counted from the pelvis (see close-up at right). Note the absence of these features in the XpdTTD / † XPCS mouse.\n(C) Quantification of relative bone mineral density of tail vertebrae from 20-mo-old male wt (n = 3), XpdTTD/†XPCS (n = 4), and XpdTTD/TTD (n = 3) mice. The p-values indicate the significance of the difference relative to XpdTTD/TTD. Error bars indicate SEM.\n(D) Body weight curves as a function of time. Note that the age-dependent cachexia observed in XpdTTD/TTD mice was rescued in both male and female XpdTTD / †XPCS mice. Significant differences between wt and XpdTTD/TTD but not between wt and XpdTTD/†XPCS mice were observed at 9 and 18 mo of age as indicated by asterisks. Error bars indicate SEM.\nTable 2 Pleiotropic Xpd Biallelic Effects in Mice and Cells To determine whether the homozygous lethal Xpd†XPCS allele was unique in its ability to ameliorate symptoms associated with the XpdTTD allele, we generated compound heterozygous XpdTTD/†XP mice by crossing the corresponding heterozygous animals."}

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3 Rescue of TTD-Associated Segmental Progeroid Features in Compound Heterozygous Xpd TTD/†XPCS Mice\n(A) Photographs of 20-mo-old wt, compound heterozygous XpdTTD/†XPCS, and homozygous XpdTTD/TTD mice. Note the extreme cachexia (lack of subcutaneous fat) in the XpdTTD/TTD mouse and the absence of this phenotype in wt and XpdTTD/†XPCS mice.\n(B) Radiographs of 20-mo-old male wt, XpdTTD/†XPCS, and XpdTTD/TTD mice. Ageing XpdTTD/TTD mice develop kyphosis (curvature of the spinal column) and reduction of bone mineral density as shown in the 6–8 segment of the tail vertebrae counted from the pelvis (see close-up at right). Note the absence of these features in the XpdTTD / † XPCS mouse.\n(C) Quantification of relative bone mineral density of tail vertebrae from 20-mo-old male wt (n = 3), XpdTTD/†XPCS (n = 4), and XpdTTD/TTD (n = 3) mice. The p-values indicate the significance of the difference relative to XpdTTD/TTD. Error bars indicate SEM.\n(D) Body weight curves as a function of time. Note that the age-dependent cachexia observed in XpdTTD/TTD mice was rescued in both male and female XpdTTD / †XPCS mice. Significant differences between wt and XpdTTD/TTD but not between wt and XpdTTD/†XPCS mice were observed at 9 and 18 mo of age as indicated by asterisks. Error bars indicate SEM.\nTable 2 Pleiotropic Xpd Biallelic Effects in Mice and Cells To determine whether the homozygous lethal Xpd†XPCS allele was unique in its ability to ameliorate symptoms associated with the XpdTTD allele, we generated compound heterozygous XpdTTD/†XP mice by crossing the corresponding heterozygous animals."}