Conditional deletion of SIRT6 in intervertebral disc accelerates age-associated degeneration. (IMAGE)
Caption
a Schematic showing Sirt6 floxed allele which following Cre-mediate recombination generates a functionally null mutant allele. b Experimental design showing the timeline of tamoxifen injection and analysis of control (Sirt6fl/fl) and sirt6 loss (Sirt6AcanCreERT2/Sirt6cKO) mouse cohorts. c Immunofluorescence staining for H3K9ac shows a robust increase in NP, AF and EP compartment of the lumbar disc confirming the deletion of SIRT6. d Safranin-O/Fast Green staining of Sirt6fl/fl and Sirt6cKO lumbar discs at 12 and 24 months. Scale bar 1A: row 1 = 200 μm; row 2 = 50 μm. e, f Distribution of and (e', f' average modified thompson's grades of lumbar discs of Sirt6fl/fl and Sirt6cKO mice analyzed at 12 and 24 months. 12 months: n = 4–6 mice/group, 3–4 discs/animal. 24 months: n = 3–6 animals/mice, 3–4 discs/animal. g-g"' Level by level average modified Thompson grading scores for NP and AF compartments of lumbar discs analyzed from 12 and 24 months Sirt6fl/fl and Sirt6cKO mice. h μCT analysis showing (i-i") Disc height (DH), Vertebral height (VB) and Disc height index (DHI) measured at 12 months and 24 months. j TUNEL staining images and (k-k") TUNEL quantitation. Statistical difference between grade distributions (e, f) was tested using chi-square test, all other quantitative data was compared using unpaired t-test, *P < 0.05.
Credit
The authors (Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria A. Tran, Shira Johnston, Maria Tsingas, Ruteja A. Barve, Ramkrishna Mitra, Richard F. Loeser, John A. Collins & Makarand V. Risbud)
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CC BY