Disruption of Ninjurin1 Leads to Repetitive and Anxiety-Like Behaviors in Mice.
Over the last few decades, molecular neurobiology has uncovered many genes whose deficiency in mice results in behavioral traits associated with human neuropsychiatric disorders such as autism, obsessive-compulsive disorder (OCD), and schizophrenia. However, the etiology of these common diseases remains enigmatic with the potential involvement of a battery of genes. Here, we report abnormal behavioral phenotypes of mice deficient in a cell adhesion molecule Ninjurin 1 (Ninj1), which are relevant to repetitive and anxiety behaviors of neuropsychiatric disorders. Ninj1 knockout (KO) mice exhibit compulsive grooming-induced hair loss and self-made lesions as well as increased anxiety-like behaviors. Histological analysis reveals that Ninj1 is predominantly expressed in cortico-thalamic circuits, and neuron-specific Ninj1 conditional KO mice manifest aberrant phenotypes similar to the global Ninj1 KO mice. Notably, the brains of Ninj1 KO mice display altered synaptic transmission in thalamic neurons as well as a reduced number of functional synapses. Moreover, the disruption of Ninj1 leads to glutamatergic abnormalities, including increased ionotropic glutamate receptors but reduced glutamate levels. Furthermore, chronic treatment with fluoxetine, a drug reportedly ameliorates compulsive behaviors in mice, prevents progression of hair loss and alleviates the compulsive grooming and anxiety-like behavior of Ninj1 KO mice. Collectively, our results suggest that Ninj1 could be involved in neuropsychiatric disorders associated with impairments of repetitive and anxiety behaviors.
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.
Hoang
H
Le
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.|Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Bum Ju
BJ
Ahn
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.
Hye Shin
HS
Lee
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, South Korea.
Anna
A
Shin
KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, South Korea.
Sujin
S
Chae
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.
Sung Yi
SY
Lee
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.
Min Wook
MW
Shin
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.
Eun-Ji
EJ
Lee
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.|Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Jong-Ho
JH
Cha
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.
Taekwon
T
Son
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.
Ji Hae
JH
Seo
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea.
Hee-Jun
HJ
Wee
College of Pharmacy, Inje University, Gimhae, 621-749, South Korea.
Hyo-Jong
HJ
Lee
Department of Psychiatry and Program in Neuroscience, McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA.
Yongwoo
Y
Jang
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Eng H
EH
Lo
Department of Life Sciences, Ewha Womans University, Seoul, 120-750, South Korea.
Sejin
S
Jeon
Department of Life Sciences, Ewha Womans University, Seoul, 120-750, South Korea.
Goo Taeg
GT
Oh
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, South Korea.
Daesoo
D
Kim
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea. qwonkim@snu.ac.kr.|Crop Biotechnology Institute, GreenBio Science and Technology, Seoul National University, Pyeongchang, 25354, South Korea. qwonkim@snu.ac.kr.
Kyu-Won
KW
Kim
D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism* / Q000523:psychology; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency* / Q000235:genetics*; D002478:Cells, Cultured; D003192:Compulsive Behavior / Q000235:genetics* / Q000378:metabolism* / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000235:genetics*
D015816:Cell Adhesion Molecules, Neuronal; D009414:Nerve Growth Factors; C484439:Ninj1 protein, mouse
Anxiety-like behavior; Fluoxetine; Glutamate receptors; Ninj1; OCD; Repetitive behavior