Trio gene is required for mouse learning ability.
Trio is a guanine nucleotide exchange factor with multiple guanine nucleotide exchange factor domains. Trio regulates cytoskeleton dynamics and actin remodeling and is involved in cell migration and axonal guidance in neuronal development. The null allele of the Trio gene led to embryonic lethality, and Trio null embryos displayed aberrant organization in several regions of the brain at E18.5, including hippocampus. Nestin-Trio-/- mice, in which the Trio gene was deleted specifically in the neuronal system by the Nestin-Cre system, displayed severe phenotypes, including low survival rate, ataxia and multiple developmental defects of the cerebellum. All Nestin-Trio-/- mice died before reaching adulthood, which hinders research on Trio gene function in adult mice. Thus, we generated EMX1-Trio-/- mice by crossing Trio-floxed mice with EMX1-Cre mice in which Cre is expressed in the brain cortex and hippocampus. EMX1-Trio-/- mice can survive to adulthood. Trio gene deletion results in smaller brains, an abnormal hippocampus and disordered granule cells in the dentate gyrus (DG) and cornu ammonis (CA). Behavior tests showed that Trio deletion interfered with the hippocampal-dependent spatial learning in the mice, suggesting that Trio plays critical roles in the learning ability of adult mice. We conclude that the Trio gene regulates the neuronal development of the hippocampus and that it affects the intelligence of adult mice.
Key Laboratory of the Ministry of Education for Experimental Teratology and School of Life Science, Shandong University, Jinan 250100, China.
Wen
W
Zong
Key Laboratory of the Ministry of Education for Experimental Teratology and School of Life Science, Shandong University, Jinan 250100, China.
Shuoyang
S
Liu
Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
Xiaotong
X
Wang
Key Laboratory of the Ministry of Education for Experimental Teratology and School of Life Science, Shandong University, Jinan 250100, China.
Jian
J
Zhang
Key Laboratory of the Ministry of Education for Experimental Teratology and School of Life Science, Shandong University, Jinan 250100, China.
Tingting
T
Zhang
Key Laboratory of the Ministry of Education for Experimental Teratology and School of Life Science, Shandong University, Jinan 250100, China.
Ziyi
Z
Liu
Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
Dongdong
D
Wang
Key Laboratory of the Ministry of Education for Experimental Teratology and School of Life Science, Shandong University, Jinan 250100, China.
Aizhen
A
Zhang
Model Animal Research Center, Key Laboratory of Model Animal for Disease Study of Ministry of Education, Nanjing University, Nanjing210061, China. Electronic address: zhums@nju.edu.cn.
Minsheng
M
Zhu
Key Laboratory of the Ministry of Education for Experimental Teratology and School of Life Science, Shandong University, Jinan 250100, China. Electronic address: jggao@sdu.edu.cn.
Jiangang
J
Gao
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D005239:Fear / Q000523:psychology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007859:Learning Disabilities / Q000235:genetics* / Q000473:pathology*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011930:Reaction Time / Q000235:genetics; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099260:Empty Spiracles Homeobox Proteins
D020662:Guanine Nucleotide Exchange Factors; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C490975:Trio protein, mouse
Hippocampus; Learning; Mouse; Trio