HnRNP U Haploinsufficiency Affects Tissue Development, Metabolic Homeostasis And Spermatogenesis In Mice

Heterogeneous nuclear ribonucleoproteins(hnRNPs)have been implicated in the control of cellular activity.Although an increasing number of hnRNPs have been identified and biochemically characterized,their biological functions,particularly in the context of an animal model,are poorly understood.Here,we firstly report a conventional knockout mouse model of hnRNP U.Hnrnpu^-/-mice are embryonic leathal before embryonice day 7.5.Hnrnpu^+/-mice are viablebut smaller when compared to wild-type littermates.In addition,Hnrnpu^+/-mice show growth retardation,decreased bone mineral density,decreased lean mass,decreased activity and food intake at night and impaired glucose homeostasis.However,Hnrnpu^+/-mice do not display abnormal behavior.Thus,our work uncovers a role for hnRNP U in a diverse group of cellular processes,including the normal growth of somatic tissues,metabolism homeostasis and activities.More and more evidences demonstrate that hnRNP U play a role in physiological processes,but little is known about their functions in spermatogenesis.Here,we report that haploinsufficiency of hnRNP U results in male infertility because of impairment of spermatogenesis.We show that Hnrnpu^+/-mice exhibit increased cell deth and decreased cell proliferation in spermatogonia.We demonstrate that haploinsufficiency of hnRNP U effect the m RNA levels of crucial genes involved in spermiogenesis and in sertoli cells.Our work provides in vivo evidence that hnRNP U has a unique role in spermatogenesis that ensures the maintenance of male fertility.This may has implications for the diagnosis and management of human male infertility.