[Abstract Title]. - Society for Neuroscience

NRG1+/- mice exhibit schizophrenia-like traits. BACE1-/- mice have been shown to have
hypomyelination that seems to be a result of impaired processing of NRG1. In addition, we
demonstrated that BACE1-/- mice exhibit multiple schizophrenia-like phenotypes including
deficits in prepulse inhibition, novelty-induced hyperactivity, hypersensitivity to a glutamatergic
psychostimulant (MK-801), working memory impairments and alterations in social interactions.
Thus, BACE1-/- mice exhibit a variety of abnormalities reminiscent of those identified in
schizophrenia that can be linked to altered BACE1-dependent NRG1 signaling. BACE2, a
homolog of BACE1, shares some substrates with BACE1 such as APP. However, only BACE1
participates in proteolyses of NRG1. Taking advantage of availability of BACE2-/- mice, we
asked whether ablation of BACE2 leads to schizophrenia-like phenotypes observed in BACE1-/-
mice. We tested a number of behaviors including novelty-induced exploration, prepulse
inhibition, spatial working memory and anxiety levels. Unlike BACE1 null mice, mice lacking
BACE2 performed similarly to wild type littermates in all of these tasks. Importantly, ablation of
BACE2 did not modify behavioral deficits occurring in BACE1-/- mice, outcomes that are
consistent with the view that BACE2 does not contribute to the BACE1-dependent pathways that
mediate schizophrenia-like behaviors occurring in BACE1 null mice.
Disclosures: J.W. Yu, None; A.V. Savonenko , None; T. Melnikova, None; H.D. Kim,
None; D.L. Price, None; P.C. Wong, None.
Poster
254. Schizophrenia: Mutant Animal Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 254.22/Y11
Topic: C.15.e. Schizophrenia: Experimental pharmacotherapeutics
Support: the Mitsubishi Pharma Research
Title: Identification of susceptibility genes for antipsychotic -induced tardive dyskinesia
Authors: *A. SYU 1 , H. ISHIGURO 2 , Y. HORIUCHI 2,3 , M. KOGA 2,3 , T. INADA 4 , M.
TAKAHASHI 5 , M. ITOKAWA 6 , A. KAKITA 7 , H. NAWA 7 , H. TAKAHASHI 7 , T.
ARINAMI 2,3 ;
1 Tsukuba Univ., 2 Tsukuba Univ., Tsukuba, Japan; 3 CREST, Wako, Japan; 4 Seiwa Hosp.,
Shinjyuku, Japan; 5 Niigata Univ., Niigata, Japan; 6 TOKYO INSTITUTE OF PSYCHIATRY,
Kodaira Tokyo, Japan; 7 Brain Reserch Institute,Niigata Univ., Niigata, Japan
Abstract: Antipsychotic -induced tardive dyskinesia (TD) is an involuntary movement disorder
that develops in patients who have undergone long-term treatment with antipsychotic