Cognitive and behavioral abnormalities in Adgrl1−/− mice
(A and B) Neurological deficits in the offspring on the mixed 129/SvJ-C57BL/6 background.
(A) Left: An example of a loss of righting reflex in a P4 HET pup, compared to its WT littermate. Center: P3 HET pup underdeveloped due to suckling problems, with its WT littermate. Right: An example of a P21 HET pup experiencing arrest and seizures after transfer into a new environment (open space).
(B) The frequency of neurodevelopmental deficits in WT, HET, and KO pups (circles, mean values; bars, ± 95% confidence intervals, CI; whiskers, ± 99% CIs. WT, n = 23; HET, n = 28 normal, 6 compromised; KO, n = 1 normal, estimated 23 dead in utero).
(C–J) Behavioral abnormalities in the Adgrl1−/− colony on the compensatory C57BL/6 background.
(C) Percent of breeding pairs of specified genotype committing parental infanticide (X = WT or HET; circles, mean values; bars, ± 95% CIs; whiskers, ± 99% CIs).
(D) Consecutive litters killed by parents of indicated genotype.
(E) Parity in breeding pairs of specified genotypes (X = WT or HET; circles, mean values; bars, ± 95% CI; all KO pairs n = 156, nulliparous n = 72; all WT pairs n = 20, nulliparous n = 4).
(F) Examples of running wheel activity of WT and KO littermates (ticks correspond to revolutions per min).
(G) Average wheel-running activity in mice of indicated genotypes (KO animals are plotted as two groups of high- or low-locomotor activity; WT or HET, n = 8; KO, n = 4 and 4).
(H) Typical auditory startle reflex responses in WT and KO mice under indicated protocols (respective individual traces overlaid). Trial types: PN, pre-pulse, no startle stimulus; NS, no pre-pulse, startle stimulus; PS, pre-pulse, startle stimulus; RIS, 1 mg/kg risperidone, 30 min prior to test. (WT animals: vehicle group, n = 6; risperidone group, n = 4; KO animals: vehicle group, n = 4; risperidone group, n = 4).
(I) Quantification of startle responses as in (H).
(J) PPI in PS trials in control and risperidone-treated animals.
(K) Overall time spent self-grooming by WT and KO mice over a 10-min period in a new environment. (WT animals, n = 9; KO animals, n = 10).
All data are the means ± SEM; ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001; NS, non-significant.