[Abstract Title]. - Society for Neuroscience

Title: Triple knockouts of the mouse vasopressin 1a, vasopressin 1b and oxytocin receptors are
fertile and useful reagents for antibody controls
Authors: *S. YOUNG 1 , H.-J. LEE 1 , G. KANNAN 1 , S. J. LOLAIT 2 , A. IACANGELO 1 , E.
SHEPARD 1 , A.-M. O'CARROLL 2 ;
1 SNGE, NIMH, NIH, DHHS, Bethesda, MD; 2 LINE, DHB, Univ. of Bristol, Bristol, United
Kingdom
Abstract: The nonapetides vasopressin (Avp) and oxytocin (Oxt) are essential for normal social
behavior in mammals. They exert their actions in the brain through three receptors - the
vasopressin 1a (Avpr1a), vasopressin 1b (Avpr1b) and oxytocin (Oxtr) receptors (1). The
development of mouse knockouts (KOs) of these receptors has greatly facilitated our
understanding of their respective roles in regulating the behaviors, as well as peripheral actions,
generated by Avp and Oxt. As we have KOs for each of the receptors (2-4), we investigated the
effects of eliminating all 3 receptors in single mice (3KOs). These 3KOs were viable with no
apparent gross physical abnormalities. Furthermore, both male and female 3KOs were fertile
when mated with C57Bl/6 mates. A 3KO female had litters at 30, 21 and 21d and a 3KO male at
20 and 28 days after matings (continuous pairing). The females were, as expected, unable to
support their pups through lactation. Also, double KOs-Single Hets (2KO1Het, Avpr1a/Avpr1b -
Oxtr) were fertile, although slightly less than normal (6.2 pups per 1st and 2nd litters at an
average of 30 days after mating with continuous pairing, range of 22-48d). Although there are
practical difficulties in obtaining enough 3KO and control mice for behavioral studies (crossfostering
C57Bl/6 pups with the 2KO1Het dams may be a suitable compromise), these mice
might be quite useful for studies of stress responses or residual CNS responses to Avp or Oxt, for
example. In addition, as the Oxtr KO is conditional, it could be selectively inactivated at a later
time. Finally, these single and multiple KOs are useful to examine the specificity of receptor
antibodies. We are in the process of screening available Avpr1b and Oxtr antibodies by western
blotting and, to date, none is effective in the mouse. We will make this data available on our
website (http://intramural.nimh.nih.gov/lcmr/snge/).
1. Caldwell, HK, Young, WS 3rd (2006) In: Handbook of Neurochemistry and Molecular
Neurobiology. pp. 573-607. Ed. R. Lim. Springer: New York.
2. Wersinger, SR, et al. (2002). Mol. Psychiat. 7, 975-984.
3. Caldwell, HK, et al. (2006) Front. Neuroendocrinol. 27, 126.
4. Lee, H-J, et al. (2008) Endocrinology Epub Mar 20.
Disclosures: S. Young , None; H. Lee, None; G. Kannan, None; S.J. Lolait, None; A.
Iacangelo, None; E. Shepard, None; A. O'Carroll, None.
Poster
291. Animal Cognition and Behavior: Learning and Memory: Pharmacology II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm