Targeted expression of human FSH receptor Asp567Gly mutant mRNA in testis of transgenic mice: role of human FSH receptor promoter.
OBJECTIVE
To specifically express the Asp567Gly human follicle-stimulating hormone receptor (FSHR) under the control of its promoter to evaluate the phenotypic consequences in the presence of normal pituitary function.


METHODS
We produced transgenic mice overexpressing the Asp567Gly human FSHR under the control of a 1.5kb 5'-flanking region fragment of its promoter.


RESULTS
Mice were phenotypically normal and fertile. In males, mRNA could be detected in the testis and the brain, indicating that the 1.5kb promoter fragment drives expression not only in the gonads. The testis weight/body weight ratio and the testosterone levels in transgenic and non-transgenic littermates were similar. By in situ hybridisation we found that the transgenic FSHR was highly expressed in Sertoli cells, spermatocytes and round spermatids. However, a radioligand receptor assay failed to show a significant difference in total FSHR binding sites in testis homogenates of transgenic and wild type animals, suggesting that the transgenic FSHR is probably not translated into functional receptor protein.


CONCLUSIONS
A 1.5kb 5'-region of the human FSHR drives mRNA expression of the transgene in the testis but leads to ectopic expression in germ cells and in the brain. No phenotypic consequences could be documented due to the lack of protein expression.
Nordhoff
Verena
V
Institute of Reproductive Medicine, University of Münster, Domagkstr. 11, D-48149 Münster, Germany.
Gromoll
Jörg
J
Foppiani
Luca
L
Luetjens
C Marc
CM
Schlatt
Stefan
S
Kostova
Elena
E
Huhtaniemi
Ilpo
I
Nieschlag
Eberhard
E
Simoni
Manuela
M
D000818:Animals; D001835:Body Weight; D001923:Brain Chemistry; D015870:Gene Expression; D018390:Gene Targeting; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016296:Mutagenesis; D009929:Organ Size; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis*; D011962:Receptors, FSH / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000737:chemistry; D013737:Testis / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
D012333:RNA, Messenger; D011962:Receptors, FSH; D013739:Testosterone