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Constitutive Germline Knockout Model Constitutive germline knockout models are generated by producing a heritable loss-of-function allele in the mouse genome, typically through complete gene disruption in embryonic stem (ES) cells followed by germline transmission or through CRISPR/Cas-mediated editing of zygotes, resulting in offspring that carry a stable null allele in all tissues

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Inhibitors such as GsMTx4 can effectively block pathological cascade reactions, but they are constrained by the low permeability barrier of the avascular intervertebral disc structure