D. Bachner et al., ENHANCED EXPRESSION OF THE MURINE FMR1 GENE DURING GERM-CELL PROLIFERATION SUGGESTS A SPECIAL FUNCTION IN BOTH THE MALE AND THE FEMALE GONAD, Human molecular genetics, 2(12), 1993, pp. 2043-2050
To elucidate the function of the FMR1 gene, we applied RNA in situ hyb
ridization to cryosections of mice from different developmental stages
. The murine Fmr-l was found transcribed in a ubiquitous manner with a
n expression pattern similar to glyceraldehyd phosphate dehydrogenase,
Gapdh, which was used as a control gene. A significant difference in
the Fmr-l expression pattern, however, was markedly enhanced expressio
n specifically confined to the testis and the fetal ovary. In the imma
ture and mature testis an elevated level of Fmr-l expression is found
in type A, spermatogonia. Expression in the testis is observed in feta
l life, reaches the highest level in the immature testis, and declines
early in adult life. In the mature ovary no specific Fmr-l expression
signal was found but enhanced levels were seen in the fetal ovary. At
this developmental stage proliferation of oogonia takes place. It is
suggested that FMR1 serves a special function during germ cell prolife
ration in males and females. These findings are discussed in the light
of the current observation that fragile X patients produce only sperm
with a premutation sized allele. Two hypotheses are put forward: (1)
In males lack of FMR1 function results in a premeiotic defect preventi
ng spermatogonia with a full mutation to reach meiosis. A fragile X mu
tation can be passed on to offsprings only as a premutation (selection
hypothesis). (2) Transition of a premutation allele to full mutation
occurs in a postzygotic stage after separation of the germ line and is
restricted to soma cells (restriction hypothesis). Expression of FMR1
in proliferating germ cells is in line with both hypothesis.