Fig. 3: Genetic ablation of Slc45a4 results in dysregulation of polyamines that does not alter nociceptor anatomy.

a, qPCR analysis of Slc45a4 mRNA along the sensory neuraxis. From left to right, sciatic nerve, DRG, spinal cord and brain; n = 4, 5, 4 and 4 mice, respectively. Norm., normalized. b, Slc45a4 mRNA is expressed in all NeuN⁺ mouse DRG neurons. n = 3 mice, 1,777 cells. c, Human SLC45A4–eGFP transfected into mouse sensory neurons localizes to the plasma membrane (observed in more than three independent experiments). d, Slc45a4-KO strategy using CRISPR–Cas9 deletion of exons 3–8. e, Slc45a4 mRNA is absent in Slc45a4-KO mice. f, Metabolomic analysis of polyamine (Put, Spd, Spm) levels. Compared with the WT, Spd is reduced in KO spinal cords (WT, n = 3; KO, n = 4; t-test, *P = 0.019), but elevated in KO serum (WT, n = 8; KO n = 7; Mann–Whitney U-test, *P = 0.014), and Put levels are elevated in KO DRGs (WT, n = 8; KO, n = 6; t-test, *P = 0.014). g, Sensory neuron subpopulation markers in WT and KO mice. h, Quantification of each subpopulation marker between WT and KO mice. WT: n = 4 mice, 1,073 (CGRP), 747 (IB4), 742 (NF200) and 167 (TH) cells; KO: n = 3 mice, 761 (GCRP), 524 (IB4), 402 (NF200) and 151 (TH) cells. Statistical analysis was performed using two-way analysis of variance (ANOVA) with post hoc Holm–Šidák test; P > 0.05. Scale bars 100 µm. i, Intraepidermal innervation in WT and KO mice. Scale bars, 50 µm. j, Quantification of total (PGP9.5⁺) and CGRP⁺ fibre density in glabrous (top) and hairy skin (bottom). n = 5 (WT) and n = 4 (KO) mice; 3–6 sections per mouse. Statistical analysis was performed using t-tests; P > 0.05. k, Hair follicle innervation, in particular for CGRP⁺ Cir-HTMRs, appears normal in Slc45a4-KO mice. Scale bars 20 µm. All data are mean ± s.e.m.

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