Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy. Mus musculus breed:C57BL/6

Spinal muscular atrophy (SMA) is caused by low levels of survival motor neuron (SMN), a multifunctional protein essential for higher eukaryotes. We utilized a mild SMA model (C/C model) to examine the impact of low SMN on growth and development of mammalian sex organs. We show impaired testis development and low fertility in C/C males. Our results revealed severe perturbations in pathways critical to C/C male reproductive organ development and function, including steroid biosynthesis, apoptosis, and spermatogenesis. Our findings uncover novel hallmarks of SMA disease progression and link SMN to general male infertility.