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  Indian J Med Microbiol
 

Figure 5: Scheme for PDMX model of male azoospermia therapy. TEX11 mutation has been identified in patients with azoospermia. To validate its pathogenic roles, mouse model with the patient-derived mutation (Tex11PM/Y mice) was derived, which recapitulated patient's pathological phenotypes and displayed meiotic arrest. SSCs isolated from the testis of the Tex11PM/Y mice were expanded in vitro. CRISPR-Cas9-mediated gene correction was employed in Tex11PM/Y SSCs and repaired SSC lines were derived through single SSC expansion, followed by whole-genome sequence to exclude the off-target mutations. The repaired SSCs were then used for transplantation to restore spermatogenesis in infertility males. PDMX model thus provides proof-of-principle evidence for curing human azoospermia carrying a single mutation that causes meiotic arrest. TEX11: testis-expressed 11; SSCs: spermatogonial stem cells; ROSI: round spermatid injection; CRISPR-Cas9: clustered regularly interspaced short palindromic repeats-CRISPR-associated endonuclease 9; PDMX: patient-derived mutation xenocorrection.

Figure 5: Scheme for PDMX model of male azoospermia therapy.<i> TEX11</i> mutation has been identified in patients with azoospermia. To validate its pathogenic roles, mouse model with the patient-derived mutation (<i>Tex11</i><sup>PM/Y</sup> mice) was derived, which recapitulated patient's pathological phenotypes and displayed meiotic arrest. SSCs isolated from the testis of the <i>Tex11</i><sup>PM/Y</sup> mice were expanded <i>in vitro</i>. CRISPR-Cas9-mediated gene correction was employed in <i>Tex11</i><sup>PM/Y</sup> SSCs and repaired SSC lines were derived through single SSC expansion, followed by whole-genome sequence to exclude the off-target mutations. The repaired SSCs were then used for transplantation to restore spermatogenesis in infertility males. PDMX model thus provides proof-of-principle evidence for curing human azoospermia carrying a single mutation that causes meiotic arrest. <i>TEX11</i>: testis-expressed 11; SSCs: spermatogonial stem cells; ROSI: round spermatid injection; CRISPR-Cas9: clustered regularly interspaced short palindromic repeats-CRISPR-associated endonuclease 9; PDMX: patient-derived mutation xenocorrection.