Khdrbs1 (also known as Sam68 or STAR) is a KH type RNA-binding protein known to be phosphorylated, arginine methylated, sumoylated and acetylated. This RNA binding protein is involved in alternative spicing, protein translation, and signal transduction.
Homozygous Khdrbs1/Sam68 null mice display a lean phenotype and are protected against dietary induced obesity (DIO). In addition, they preserve their bone mass with age and do not develop age-induced osteoporosis. Offspring from heterozygote intercrosses exhibit a Mendelian segregation, but some of the homozygous pups die at birth of unknown causes. Homozygotes that survive the perinatal period frequently live to old age (> 2 years).
Ablation of the Khdrbs1 gene leads to male infertility due to several defects in spermatogenesis. Homozygous females are subfertile, exhibiting uterine development defects and delayed mammary gland development. They also fail to care for their young successfully.
Haploinsufficiency of the Khdrbs1 impedes mammary tumor onset in vivo and metastasis driven by the potent mammary-targeted polyoma middle T-antigen (MMTV-PyMT) oncogene.
Homozygous Khdrbs1 knockout mice exhibit motor coordination defects as assessed by beam walking and rotorod performance. Forelimb strength is normal, as is tail-hang reflex, balance test, grid walking, the Morris water task, recognition memory, visual discrimination, auditory stimulation and conditional taste aversion.
