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. 2021 Nov 22;41(1):e106459. doi: 10.15252/embj.2020106459

Figure 1. Setd1b is required for hippocampus‐dependent memory.

Figure 1

  1. qPCR analysis shows loss of Setd1b in forebrain regions while levels in the cerebellum are not affected (CA: Control, n = 6; cKO, n = 6. DG: Control, n = 6; cKO, n = 6. Cortex: Control, n = 7; cKO, n = 7. Cerebellum: Control, n = 4; cKO, n = 4). *P‐value < 0.05 (Student's t‐test).
  2. Immunoblot analysis shows loss of Setd1b protein in the hippocampus of Setd1b cKO mice (Control, n = 4; cKO, n = 4). **P‐value < 0.01 (Student's t‐test).
  3. Immunohistochemical staining (upper level) for marker proteins of neuronal integrity and quantification (lower panel) show no difference in control and Setd1b cKO mice (NeuN: Control, n = 6; cKO, n = 6; Student's t‐test P‐value = 0.57. MAP2: Control, n = 4; cKO, n = 4; Student's t‐test P‐value = 0.72. Iba1: Control, n = 5; cKO, n = 5; Student's t‐test P‐value = 0.8. Gfap: Control, n = 5; cKO, n = 5; Student's t‐test P‐value = 0.09.). Scale bar: 100 µm.
  4. Average speed (left panel) and percent time spent in the center (right panel) during exposure to the open field test was similar in control and Setd1b cKO mice (Average speed: Control, n = 15; cKO, n = 15; Student's t‐test P‐value = 0.075. Time spent in center: Control, n = 15; cKO, n = 15; Student's t‐test P‐value = 0.96).
  5. Short‐term memory was not different between control and Setd1b cKO mice as indicated by similar percent of alternations in the Y‐maze test (Control, n = 15; cKO, n = 15; Student's t‐test P‐value = 0.3).
  6. Depressive‐like behavior was measured in the Porsolt‐forced swim test. There was no significant difference in the % time spent immobile between groups (Control, n = 8; cKO, n = 8; Student's t‐test P‐value = 0.5).
  7. Escape latency during water maze training indicated severe learning impairment in Setd1b cKO mice (Control: n = 15, cKO: n = 15. Repeated measures ANOVA, genotype effect: F(1,28) = 82.34, ****P‐value < 0.0001).
  8. Plots showing the specific search strategies during water maze training. Note the failure of Setd1b cKO mice to adopt hippocampus‐dependent search strategies.
  9. The cognitive score calculated on the basis of the hippocampal search strategies reflects severe memory impairment in Setd1b cKO mice (Student's t‐test: ***P‐value < 0.001).

Data information: Bar graphs indicate mean, Error bars indicate ± SEM, “n” indicates biological replicates.

Source data are available online for this figure.