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Rex1 (Zfp42) null mice show impaired testicular function, abnormal testis morphology, and aberrant gene expression.

ABSTRACT: Rex1 (Zfp42), GeneID 132625, is a gene whose expression is closely associated with pluripotency/multipotency in both mouse and human embryonic stem cells. To study the function of the murine Rex1 gene in vivo, we have used cre/lox technology to create Rex1(floxed) mice and mice deficient in Rex1 gene function. Rex1(-/-)males are characterized by an age-associated decrease in sperm counts, abnormal sperm morphology, and mild testicular atrophy. We characterized global patterns of gene expression in primary germ cells by microarray and identified the growth hormone responsive gene, GRTP1, as a transcript present at a 4.5 fold higher level in wild type (WT) compared to Rex1(-/-) mice. We analyzed immature germ cell (Dazl), proliferating (PCNA), and Sertoli cell populations, and quantitated levels of apoptosis in Rex1(-/-) as compared to WT testes. We evaluated the expression of proteins previously reported to correlate with Rex1 expression, such as STAT3, phospho-STAT3, p38, and phospho-p38 in the testis. We report a distinct cellular localization of total STAT3 protein in Rex1(-/-) affected testes. Our data suggest that loss of Rex1 leads to impaired testicular function.

SUBMITTER: Rezende NC

PROVIDER: S-EPMC3214085 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Rex1 (Zfp42) null mice show impaired testicular function, abnormal testis morphology, and aberrant gene expression.

Rezende Naira C NC Lee Mi-Young MY Monette Sébastien S Mark Willie W Lu Ailan A Gudas Lorraine J LJ

Developmental biology 20110527 2

Rex1 (Zfp42), GeneID 132625, is a gene whose expression is closely associated with pluripotency/multipotency in both mouse and human embryonic stem cells. To study the function of the murine Rex1 gene in vivo, we have used cre/lox technology to create Rex1(floxed) mice and mice deficient in Rex1 gene function. Rex1(-/-)males are characterized by an age-associated decrease in sperm counts, abnormal sperm morphology, and mild testicular atrophy. We characterized global patterns of gene expression ...[more]

PMID: 21641340

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Project description:Neuronal polarity is involved in multiple developmental stages, including cortical neuron migration, multipolar-to-bipolar transition, axon initiation, apical/basal dendrite differentiation, and spine formation. All of these processes are associated with the cytoskeleton and are regulated by precise timing and by controlling gene expression. The P-Rex1 (phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1) gene for example, is known to be important for cytoskeletal reorganization, cell motility, and migration. Deficiency of P-Rex1 protein leads to abnormal neuronal migration and synaptic plasticity, as well as autism-related behaviors. Nonetheless, the effects of P-Rex1 overexpression on neuronal development and higher brain functions remain unclear. In the present study, we explored the effect of P-Rex1 overexpression on cerebral development and psychosis-related behaviors in mice. In utero electroporation at embryonic day 14.5 was used to assess the influence of P-Rex1 overexpression on cell polarity and migration. Primary neuron culture was used to explore the effects of P-Rex1 overexpression on neuritogenesis and spine morphology. In addition, P-Rex1 overexpression in the medial prefrontal cortex (mPFC) of mice was used to assess psychosis-related behaviors. We found that P-Rex1 overexpression led to aberrant polarity and inhibited the multipolar-to-bipolar transition, leading to abnormal neuronal migration. In addition, P-Rex1 overexpression affected the early development of neurons, manifested as abnormal neurite initiation with cytoskeleton change, reduced the axon length and dendritic complexity, and caused excessive lamellipodia in primary neuronal culture. Moreover, P-Rex1 overexpression decreased the density of spines with increased height, width, and head area in vitro and in vivo. Behavioral tests showed that P-Rex1 overexpression in the mouse mPFC caused anxiety-like behaviors and a sensorimotor gating deficit. The appropriate P-Rex1 level plays a critical role in the developing cerebral cortex and excessive P-Rex1 might be related to psychosis-related behaviors.

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Rex1 (Zfp42) null mice show impaired testicular function, abnormal testis morphology, and aberrant gene expression.

Publications

Rex1 (Zfp42) null mice show impaired testicular function, abnormal testis morphology, and aberrant gene expression.

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