GnRH pre-mRNA splicing: solving the mystery of a nature's knockout, hpg mouse.
The hypogonadal (hpg) mouse represents a unique animal model for hypogonadism. In this mutant the truncation of the gene encoding gonadotropin-releasing hormone (GnRH) leads to drastically lowered gonadotropin levels and prepubertal gonads. The deletional mutation encompasses only the distal half of the gene leaving the region encoding GnRH decapeptide intact. The partially deleted gene is transcriptionally active, but translationally inactive. Even though several aspects have been considered to account for the phenomenon, there is no satisfactory explanation so far. Recent reports showed that excision of the GnRH first intron is delicately regulated in a cell type- and developmental stage-specific manner mediated by putative-specific splicing factors acting on cis-acting elements located in exon 3 and 4, and is significantly decreased in hpg mouse whose exonic splicing enhancers are absent. Furthermore, the suppressing effect of intron A retention on the translational activity of downstream open reading frame was reported, giving an insight into the understanding the mystery of hpg mice.
Son
Gi Hoon
GH
School of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Park
Eonyoung
E
Jung
Hosung
H
Han
Jin
J
Lee
Kun Ho
KH
Seong
Jae Young
JY
Kim
Kyungjin
K
D000818:Animals; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D007438:Introns / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone