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<p>Among small ruminants, natural bovine spongiform encephalopathy (BSE) has been confirmed only in goats, raising concern about the possible entry of caprine BSE into the food chain. Genetic selection for <i>PRNP</i> alleles associated with resistance to classical scrapie, particularly K<sub>222</sub> and S<sub>127</sub>, has been proposed as a control strategy, but their effect on caprine BSE is unclear. Nine Alpine goats carrying different <i>PRNP</i> genotypes at codons <sub>222</sub> (Q/Q, Q/K, K/K) and <sub>127</sub> (G/G, G/S) were intracerebrally inoculated with a second-passage caprine BSE isolate and monitored until terminal disease or censoring. Brain and selected peripheral tissues were examined for PrP<sup>Sc</sup> by immunohistochemistry, western blotting, and conformation-dependent immunoassay, and lesion severity and PrP<sup>Sc</sup> distribution were compared among genotypes. All goats lacking the S<sub>127</sub> allele developed clinical disease with widespread PrP<sup>Sc</sup> accumulation in the central nervous system. Compared with Q/Q<sub>222</sub> goats, Q/K<sub>222</sub> and K/K<sub>222</sub> goats showed longer incubation periods and lower overall PrP<sup>Sc</sup> and vacuolation scores, although disease still occurred in both genotypes after intracerebral challenge. Two G/S<sub>127</sub> goats, one Q/Q<sub>222</sub> and one Q/K<sub>222</sub>, remained clinically healthy and biopsy-negative at &gt; 1400&#xa0;days post-inoculation, but were right-censored because they were alive at last follow-up and had not undergone post&#xa0;mortem examination. PrP<sup>Sc</sup> was also variably detected in lymphoreticular tissues and in the enteric and peripheral nervous systems, irrespective of genotype. Under these stringent challenge conditions, K<sub>222</sub> delays disease onset but does not confer complete resistance. The prolonged survival of S<sub>127</sub> carriers remains a preliminary, censored observation requiring post mortem confirmation.</p>

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Incomplete protection of the K222 polymorphism of the prion protein gene after intracerebral exposure to caprine BSE in goats: preliminary follow-up in S127 carriers

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月30日

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  • Diego Sola,
  • José-Luis Pitarch,
  • Belén Marín,
  • Helen-Caroline Raksa,
  • Alicia Otero,
  • Francis Barillet,
  • Frederic Bouvier,
  • Rosa Bolea,
  • Alex Bossers,
  • Olivier Andreoletti,
  • Jan Langeveld,
  • Juan-José Badiola,
  • Cristina Acín

摘要

Among small ruminants, natural bovine spongiform encephalopathy (BSE) has been confirmed only in goats, raising concern about the possible entry of caprine BSE into the food chain. Genetic selection for PRNP alleles associated with resistance to classical scrapie, particularly K222 and S127, has been proposed as a control strategy, but their effect on caprine BSE is unclear. Nine Alpine goats carrying different PRNP genotypes at codons 222 (Q/Q, Q/K, K/K) and 127 (G/G, G/S) were intracerebrally inoculated with a second-passage caprine BSE isolate and monitored until terminal disease or censoring. Brain and selected peripheral tissues were examined for PrPSc by immunohistochemistry, western blotting, and conformation-dependent immunoassay, and lesion severity and PrPSc distribution were compared among genotypes. All goats lacking the S127 allele developed clinical disease with widespread PrPSc accumulation in the central nervous system. Compared with Q/Q222 goats, Q/K222 and K/K222 goats showed longer incubation periods and lower overall PrPSc and vacuolation scores, although disease still occurred in both genotypes after intracerebral challenge. Two G/S127 goats, one Q/Q222 and one Q/K222, remained clinically healthy and biopsy-negative at > 1400 days post-inoculation, but were right-censored because they were alive at last follow-up and had not undergone post mortem examination. PrPSc was also variably detected in lymphoreticular tissues and in the enteric and peripheral nervous systems, irrespective of genotype. Under these stringent challenge conditions, K222 delays disease onset but does not confer complete resistance. The prolonged survival of S127 carriers remains a preliminary, censored observation requiring post mortem confirmation.