Macroorchidism in FMR1 knockout mice is caused by increased Sertoli cell proliferation during testicular development.

Abstract:

:The fragile X syndrome is the most frequent hereditary form of mental retardation. This X-linked disorder is, in most cases, caused by an unstable and expanding trinucleotide CGG repeat located in the 5'-untranslated region of the gene involved, the fragile X mental retardation 1 (FMR1) gene. Expansion of the CGG repeat to a length of more than 200 trinucleotides results in silencing of the FMR1 gene promoter and, thus, in an inactive gene. The clinical features of male fragile X patients include mental retardation, autistiform behavior, and characteristic facial features. In addition, macroorchidism is observed. To study the role of Sertoli cell proliferation and FSH signal transduction in the occurrence of macroorchidism in fragile X males, we made use of an animal model for the fragile X syndrome, an Fmr1 knockout mouse. The results indicate that in male Fmr1 knockout mice, the rate of Sertoli cell proliferation is increased from embryonic day 12 to 15 days postnatally. The onset and length of the period of Sertoli cell proliferation were not changed compared with those in the control males. Serum levels of FSH, FSH receptor messenger RNA expression, and short term effects of FSH on Sertoli cell function, as measured by down-regulation of FSH receptor messenger RNA, were not changed. We conclude that macroorchidism in Fmr1 knockout male mice is caused by an increased rate of Sertoli cell proliferation. This increase does not appear to be the result of a major change in FSH signal transduction in Fmr1 knockout mice.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Slegtenhorst-Eegdeman KE,de Rooij DG,Verhoef-Post M,van de Kant HJ,Bakker CE,Oostra BA,Grootegoed JA,Themmen AP

doi

10.1210/endo.139.1.5706

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

156-62

issue

1

eissn

0013-7227

issn

1945-7170

journal_volume

139

pub_type

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