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Mice deficient for testis-brain RNA-binding protein exhibit a coordinate loss of TRAX, reduced fertility, altered gene expression in the brain, and behavioral changes
Journal article   Peer reviewed

Mice deficient for testis-brain RNA-binding protein exhibit a coordinate loss of TRAX, reduced fertility, altered gene expression in the brain, and behavioral changes

Vargheese Chennathukuzhi, Joel M Stein, Ted Abel, Stacy Donlon, Shicheng Yang, Juli P Miller, David M Allman, Rebecca A Simmons and Norman B Hecht
Molecular and cellular biology, Vol.23(18), pp.6419-6434
09/2003
DOI: 10.1128/MCB.23.18.6419-6434.2003
PMCID: PMC193699
PMID: 12944470

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Abstract

Testis-brain RNA-binding protein (TB-RBP), the mouse orthologue of the human protein Translin, is a widely expressed and highly conserved protein with proposed functions in chromosomal translocations, mitotic cell division, and mRNA transport and storage. To better define the biological roles of TB-RBP, we generated mice lacking TB-RBP. Matings between heterozygotes gave rise to viable, apparently normal homozygous mutant mice at a normal Mendelian ratio. The TB-RBP-related and -interacting protein Translin-associated factor X was reduced to 50% normal levels in heterozygotes and was absent in TB-RBP-null animals. The null mice were 10 to 30% smaller than their wild-type or heterozygote littermates at birth and remained so to about 6 to 9 months of age, showed normal B- and T-cell development, and accumulated visceral fat. TB-RBP-null male mice were fertile and sired offspring but had abnormal seminiferous tubules and reduced sperm counts. Null female mice were subfertile and had reduced litter sizes. Microarray analysis of total brain RNA from null and wild-type mice revealed an altered gene expression profile with the up-regulation of 14 genes and the down-regulation of 217 genes out of 12,473 probe sets. Numerous neurotransmitter receptors and ion channels, including gamma-aminobutyric acid A receptor alpha1 and glutamate receptor alpha3, were strongly down-regulated. Behavioral abnormalities were also seen. Compared to littermates, the TB-RBP-null mice appeared docile and exhibited reduced Rota-Rod performance.
 Sperm Count T-Lymphocytes - physiology Spermatogenesis - genetics Oligonucleotide Array Sequence Analysis Male Gene Expression Profiling Luteinizing Hormone - metabolism RNA-Binding Proteins Brain - physiology DNA-Binding Proteins - deficiency Seminal Vesicles - physiology Behavior, Animal Body Constitution - genetics DNA-Binding Proteins - metabolism Fertility - genetics Mice, Mutant Strains Female Bacterial Outer Membrane Proteins - genetics Litter Size Follicle Stimulating Hormone - metabolism Mice, Inbred C57BL Gene Expression Regulation B-Lymphocytes - physiology DNA-Binding Proteins - genetics Birth Weight - genetics Animals Bacterial Outer Membrane Proteins - metabolism Mice

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