Effect of NLRP6 gene knockout on growth and reproduction and parenchymal organs in mice

Abstract:

Objective NLRP6（NOD-like receptor thermal protein domain associated protein 6），a recently identified member of the nucleotide-binding oligomerization domain（NOD）-like receptors family，is abundantly expressed in the intestine，liver，kidney，spleen，muscle，and other tissues or organs，playing a regulatory role in various biological processes such as inflammation，pyroptosis，and autophagy. Recently，NLRP6 was reported to exert a significant impact on the disease phenotypes of various tissues and organs under stress conditions. However，the role of NLRP6 in the growth and development of tissues and organs in a natural state remains unclear.Methods A mouse model of NLRP6 gene knockout was established using CRISPR/Cas9 gene editing technique. The mice were raised and observed for their growth and reproduction. The spleen，liver，heart，kidney，brain，limbs，and dorsal skin of the mice were dissected，sectioned，and stained to evaluate the effect of NLRP6 gene knockout on the macroscopic development of parenchymal organs and microscopic tissue structure.Results In the natural state，NLRP6 knockout shortened the sexual maturity in male mice，resulting in irreversible ulceration and atrophy of the testicles in adult male mice. NLRP6 gene knockout led to the rupture of striated muscle in the hindlimbs in adult male mice，resulting in obvious atrophy of the hindlimbs. NLRP6 gene knockout not only significantly increased the volume of the spleen（P<0.01）but also induced inflammatory cell infiltration in male mice. NLRP6 gene knockout caused significant ulcerous damage，collagen fiber proliferation，and inflammatory cell infiltration in the dorsal skin in male mice.Conclusion In the natural condition of growth and development，NLRP6 gene knockout selectively affects genital development and sexual maturity，hindlimb muscle development，the size and immune response of the spleen，and the structural integrity of the dorsal skin in mice. This effect is significantly androgen-dependent.