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( a ) Schematic of trial epochs comprising the delayed non-match-to-sample (DNMS) SWM task. ( b i ) Days to reach criterion performance of ≥70% correct trials for three consecutive days on the DNMS SWM task in female and male WT and <t>Setd1a</t> +/– mice (n=15-22); Two-way ANOVA: Main effect of Genotype: F (1,69)=0.00, p =0.999; Main effect of Sex: F (1,69)=2.417, p =0.125; Genotype X Sex interaction: F (1,69)=1.889, p =0.174). ( b ii ) Average accuracy during training in female and male WT and Setd1a +/– mice. Two-way ANOVA: Main effect of Genotype: F (1,69)=0.569, p =0.453; Main effect of Sex: F (1,69)=1.209, p =0.275; Genotype X Sex interaction: F (1,69)=0.727, p =0.397). ( c-d ) Accuracy during testing with varying interleaved (within-session) delay lengths ( c ) and blocked (between-session) delay lengths ( d ) in female and male WT and Setd1a +/– mice. Interleaved: 3-way ANOVA, Main effect of Delay: F(2,136)=36.36, p<0.0001; n=15-22. Blocked: Mixed-effects model, Main effect of Delay: F (2,117)=40.20, p<0.0001; Delay x Genotype interaction: F (2,117)=3.110, p<0.05; WT vs. Setd1a +/– at 10-sec delay: *p<0.01, Šídák’s test; n=13-21. ( e ) Difference in performance during 10-sec delay trials between Blocked and Interleaved testing. 2-way ANOVA, Main effect of Genotype: F(1,59)=7.019, *p<0.05).
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( a ) Schematic of trial epochs comprising the delayed non-match-to-sample (DNMS) SWM task. ( b i ) Days to reach criterion performance of ≥70% correct trials for three consecutive days on the DNMS SWM task in female and male WT and Setd1a +/– mice (n=15-22); Two-way ANOVA: Main effect of Genotype: F (1,69)=0.00, p =0.999; Main effect of Sex: F (1,69)=2.417, p =0.125; Genotype X Sex interaction: F (1,69)=1.889, p =0.174). ( b ii ) Average accuracy during training in female and male WT and Setd1a +/– mice. Two-way ANOVA: Main effect of Genotype: F (1,69)=0.569, p =0.453; Main effect of Sex: F (1,69)=1.209, p =0.275; Genotype X Sex interaction: F (1,69)=0.727, p =0.397). ( c-d ) Accuracy during testing with varying interleaved (within-session) delay lengths ( c ) and blocked (between-session) delay lengths ( d ) in female and male WT and Setd1a +/– mice. Interleaved: 3-way ANOVA, Main effect of Delay: F(2,136)=36.36, p<0.0001; n=15-22. Blocked: Mixed-effects model, Main effect of Delay: F (2,117)=40.20, p<0.0001; Delay x Genotype interaction: F (2,117)=3.110, p<0.05; WT vs. Setd1a +/– at 10-sec delay: *p<0.01, Šídák’s test; n=13-21. ( e ) Difference in performance during 10-sec delay trials between Blocked and Interleaved testing. 2-way ANOVA, Main effect of Genotype: F(1,59)=7.019, *p<0.05).

Journal: bioRxiv

Article Title: Altered thalamo-prefrontal synchrony dynamics during spatial working memory task performance in a SETD1A loss-of-function mouse model of schizophrenia predisposition

doi: 10.64898/2026.01.29.702577

Figure Lengend Snippet: ( a ) Schematic of trial epochs comprising the delayed non-match-to-sample (DNMS) SWM task. ( b i ) Days to reach criterion performance of ≥70% correct trials for three consecutive days on the DNMS SWM task in female and male WT and Setd1a +/– mice (n=15-22); Two-way ANOVA: Main effect of Genotype: F (1,69)=0.00, p =0.999; Main effect of Sex: F (1,69)=2.417, p =0.125; Genotype X Sex interaction: F (1,69)=1.889, p =0.174). ( b ii ) Average accuracy during training in female and male WT and Setd1a +/– mice. Two-way ANOVA: Main effect of Genotype: F (1,69)=0.569, p =0.453; Main effect of Sex: F (1,69)=1.209, p =0.275; Genotype X Sex interaction: F (1,69)=0.727, p =0.397). ( c-d ) Accuracy during testing with varying interleaved (within-session) delay lengths ( c ) and blocked (between-session) delay lengths ( d ) in female and male WT and Setd1a +/– mice. Interleaved: 3-way ANOVA, Main effect of Delay: F(2,136)=36.36, p<0.0001; n=15-22. Blocked: Mixed-effects model, Main effect of Delay: F (2,117)=40.20, p<0.0001; Delay x Genotype interaction: F (2,117)=3.110, p<0.05; WT vs. Setd1a +/– at 10-sec delay: *p<0.01, Šídák’s test; n=13-21. ( e ) Difference in performance during 10-sec delay trials between Blocked and Interleaved testing. 2-way ANOVA, Main effect of Genotype: F(1,59)=7.019, *p<0.05).

Article Snippet: Setd1a tm1a(EUCOMM)Wtsi mice (referred to as Setd1a +/– ) were backcrossed for over 10 generations with C57BL/6J mice (The Jackson Laboratory, Bar Harbor, ME) in the laboratory of J.

Techniques:

( a-d ) Functional coefficient estimates of the Genotype covariate from FLMM of epoch-level coherence for dHPC-mPFC ( a ), vHPC-mPFC ( b ), vHPC-Re ( c ), and Re-mPFC ( d ) brain region pairs for the sample ( i, ii ), delay ( iii, iv ), and choice ( v, vi ) epochs. Functional intercept estimates ( i, iii, v ) and Genotype coefficient estimates ( ii, iv, vi ) are presented for each region pair. Genotype coefficient estimates show the difference in average coherence at each frequency between Setd1a +/– and WT mice. Pointwise and joint 95% confidence intervals (CI) are shown. Significant reductions (joint CIs do not contain zero) at specific frequencies are denoted by a red bar.

Journal: bioRxiv

Article Title: Altered thalamo-prefrontal synchrony dynamics during spatial working memory task performance in a SETD1A loss-of-function mouse model of schizophrenia predisposition

doi: 10.64898/2026.01.29.702577

Figure Lengend Snippet: ( a-d ) Functional coefficient estimates of the Genotype covariate from FLMM of epoch-level coherence for dHPC-mPFC ( a ), vHPC-mPFC ( b ), vHPC-Re ( c ), and Re-mPFC ( d ) brain region pairs for the sample ( i, ii ), delay ( iii, iv ), and choice ( v, vi ) epochs. Functional intercept estimates ( i, iii, v ) and Genotype coefficient estimates ( ii, iv, vi ) are presented for each region pair. Genotype coefficient estimates show the difference in average coherence at each frequency between Setd1a +/– and WT mice. Pointwise and joint 95% confidence intervals (CI) are shown. Significant reductions (joint CIs do not contain zero) at specific frequencies are denoted by a red bar.

Article Snippet: Setd1a tm1a(EUCOMM)Wtsi mice (referred to as Setd1a +/– ) were backcrossed for over 10 generations with C57BL/6J mice (The Jackson Laboratory, Bar Harbor, ME) in the laboratory of J.

Techniques: Functional Assay

( a ) Average dHPC-mPFC coherence spectra from WT ( a i ) and Setd1a +/– ( a ii ) mice during sample, delay, and choice epochs of 10-sec delay trials in Blocked testing in the SWM task. ( b ) FLMM of Genotype and Epoch covariate effects on epoch-level dHPC-mPFC coherence data during delay (D) relative to sample (S; b i , b iii ) or choice (C; b ii , b iv ) epochs. ( b i , b ii ) Functional coefficient estimates of the Epoch covariate in WT mice, showing differences in the average dHPC-mPFC coherence at each frequency between epoch types. ( b iii , b iv ) Functional coefficient estimates of the interaction between the Genotype x Epoch covariates, showing how differences in the average dHPC-mPFC coherence at each frequency between epoch types differ between WT and Setd1a +/– mice. Significant reductions (joint CIs do not contain zero) at specific frequencies are denoted by red bars. n=19 WT, 22 Setd1a +/– mice.

Journal: bioRxiv

Article Title: Altered thalamo-prefrontal synchrony dynamics during spatial working memory task performance in a SETD1A loss-of-function mouse model of schizophrenia predisposition

doi: 10.64898/2026.01.29.702577

Figure Lengend Snippet: ( a ) Average dHPC-mPFC coherence spectra from WT ( a i ) and Setd1a +/– ( a ii ) mice during sample, delay, and choice epochs of 10-sec delay trials in Blocked testing in the SWM task. ( b ) FLMM of Genotype and Epoch covariate effects on epoch-level dHPC-mPFC coherence data during delay (D) relative to sample (S; b i , b iii ) or choice (C; b ii , b iv ) epochs. ( b i , b ii ) Functional coefficient estimates of the Epoch covariate in WT mice, showing differences in the average dHPC-mPFC coherence at each frequency between epoch types. ( b iii , b iv ) Functional coefficient estimates of the interaction between the Genotype x Epoch covariates, showing how differences in the average dHPC-mPFC coherence at each frequency between epoch types differ between WT and Setd1a +/– mice. Significant reductions (joint CIs do not contain zero) at specific frequencies are denoted by red bars. n=19 WT, 22 Setd1a +/– mice.

Article Snippet: Setd1a tm1a(EUCOMM)Wtsi mice (referred to as Setd1a +/– ) were backcrossed for over 10 generations with C57BL/6J mice (The Jackson Laboratory, Bar Harbor, ME) in the laboratory of J.

Techniques: Functional Assay

( a ) Average Re-mPFC coherence spectra from WT ( a i ) and Setd1a +/– ( a ii ) mice during sample, delay, and choice epochs of 10-sec delay trials in Blocked testing in the SWM task. ( b ) FLMM of Genotype and Epoch covariate effects on epoch-level Re-mPFC coherence data during delay (D) relative to sample (S; b i , b iii ) or choice (C; b ii , b iv ) epochs. ( b i , b ii ) Functional coefficient estimates of the Epoch covariate in WT mice, showing differences in the average Re-mPFC coherence at each frequency between epoch types. ( b iii , b iv ) Functional coefficient estimates of the interaction between the Genotype x Epoch covariates, showing how differences in the average Re-mPFC coherence at each frequency between epoch types differ between WT and Setd1a +/– mice. Significant enhancements and reductions (joint CIs do not contain zero) at specific frequencies are denoted by green and red bars, respectively. n=19 WT, 23 Setd1a +/– mice.

Journal: bioRxiv

Article Title: Altered thalamo-prefrontal synchrony dynamics during spatial working memory task performance in a SETD1A loss-of-function mouse model of schizophrenia predisposition

doi: 10.64898/2026.01.29.702577

Figure Lengend Snippet: ( a ) Average Re-mPFC coherence spectra from WT ( a i ) and Setd1a +/– ( a ii ) mice during sample, delay, and choice epochs of 10-sec delay trials in Blocked testing in the SWM task. ( b ) FLMM of Genotype and Epoch covariate effects on epoch-level Re-mPFC coherence data during delay (D) relative to sample (S; b i , b iii ) or choice (C; b ii , b iv ) epochs. ( b i , b ii ) Functional coefficient estimates of the Epoch covariate in WT mice, showing differences in the average Re-mPFC coherence at each frequency between epoch types. ( b iii , b iv ) Functional coefficient estimates of the interaction between the Genotype x Epoch covariates, showing how differences in the average Re-mPFC coherence at each frequency between epoch types differ between WT and Setd1a +/– mice. Significant enhancements and reductions (joint CIs do not contain zero) at specific frequencies are denoted by green and red bars, respectively. n=19 WT, 23 Setd1a +/– mice.

Article Snippet: Setd1a tm1a(EUCOMM)Wtsi mice (referred to as Setd1a +/– ) were backcrossed for over 10 generations with C57BL/6J mice (The Jackson Laboratory, Bar Harbor, ME) in the laboratory of J.

Techniques: Functional Assay

( a ) Representative histology showing electrode placements in mPFC, vHPC, dHPC, and Re. Yellow arrows indicate the estimated electrode termination sites. Scale bars = 500μm. ( b ) Electrode placements in mPFC, vHPC, dHPC, and Re of female and male WT and Setd1a +/– mice.

Journal: bioRxiv

Article Title: Altered thalamo-prefrontal synchrony dynamics during spatial working memory task performance in a SETD1A loss-of-function mouse model of schizophrenia predisposition

doi: 10.64898/2026.01.29.702577

Figure Lengend Snippet: ( a ) Representative histology showing electrode placements in mPFC, vHPC, dHPC, and Re. Yellow arrows indicate the estimated electrode termination sites. Scale bars = 500μm. ( b ) Electrode placements in mPFC, vHPC, dHPC, and Re of female and male WT and Setd1a +/– mice.

Article Snippet: Setd1a tm1a(EUCOMM)Wtsi mice (referred to as Setd1a +/– ) were backcrossed for over 10 generations with C57BL/6J mice (The Jackson Laboratory, Bar Harbor, ME) in the laboratory of J.

Techniques:

( a ) Average vHPC-mPFC coherence spectra from WT ( a i ) and Setd1a +/– ( a ii ) mice during sample, delay, and choice epochs of 10-sec delay trials in Blocked testing in the SWM task. ( b ) FLMM of Genotype and Epoch covariate effects on epoch-level vHPC-mPFC coherence data during delay (D) relative to sample (S; b i , b iii ) or choice (C; b ii , b iv ) epochs ( b i , b ii ) Functional coefficient estimates of the Epoch covariate in WT mice, showing differences in the average vHPC-mPFC coherence at each frequency between epoch types. ( b iii , b iv ) Functional coefficient estimates of the interaction between the Genotype x Epoch covariates, showing how differences in the average vHPC-mPFC coherence at each frequency between epoch types differ between WT and Setd1a +/– mice. Significant enhancements and reductions (joint CIs do not contain zero) at specific frequencies are denoted by green and red bars, respectively. n=16 WT, 20 Setd1a +/– mice.

Journal: bioRxiv

Article Title: Altered thalamo-prefrontal synchrony dynamics during spatial working memory task performance in a SETD1A loss-of-function mouse model of schizophrenia predisposition

doi: 10.64898/2026.01.29.702577

Figure Lengend Snippet: ( a ) Average vHPC-mPFC coherence spectra from WT ( a i ) and Setd1a +/– ( a ii ) mice during sample, delay, and choice epochs of 10-sec delay trials in Blocked testing in the SWM task. ( b ) FLMM of Genotype and Epoch covariate effects on epoch-level vHPC-mPFC coherence data during delay (D) relative to sample (S; b i , b iii ) or choice (C; b ii , b iv ) epochs ( b i , b ii ) Functional coefficient estimates of the Epoch covariate in WT mice, showing differences in the average vHPC-mPFC coherence at each frequency between epoch types. ( b iii , b iv ) Functional coefficient estimates of the interaction between the Genotype x Epoch covariates, showing how differences in the average vHPC-mPFC coherence at each frequency between epoch types differ between WT and Setd1a +/– mice. Significant enhancements and reductions (joint CIs do not contain zero) at specific frequencies are denoted by green and red bars, respectively. n=16 WT, 20 Setd1a +/– mice.

Article Snippet: Setd1a tm1a(EUCOMM)Wtsi mice (referred to as Setd1a +/– ) were backcrossed for over 10 generations with C57BL/6J mice (The Jackson Laboratory, Bar Harbor, ME) in the laboratory of J.

Techniques: Functional Assay

( a ) Average vHPC-Re coherence spectra from WT ( a i ) and Setd1a +/– ( a ii ) mice during sample, delay, and choice epochs of 10-sec delay trials in Blocked testing in the SWM task. ( b ) FLMM of Genotype and Epoch covariate effects on epoch-level vHPC-Re coherence data during delay (D) relative to sample (S; b i , b iii ) or choice (C; b ii , b iv ) epochs. ( b i , b ii ) Functional coefficient estimates of the Epoch covariate in WT mice, showing differences in the average vHPC-Re coherence at each frequency between epoch types. ( b iii , b iv ) Functional coefficient estimates of the interaction between the Genotype x Epoch covariates, showing how differences in the average vHPC-Re coherence at each frequency between epoch types differ between WT and Setd1a +/– mice. Significant enhancements and reductions (joint CIs do not contain zero) at specific frequencies are denoted by green and red bars, respectively. n=14 WT, 25 Setd1a +/– mice.

Journal: bioRxiv

Article Title: Altered thalamo-prefrontal synchrony dynamics during spatial working memory task performance in a SETD1A loss-of-function mouse model of schizophrenia predisposition

doi: 10.64898/2026.01.29.702577

Figure Lengend Snippet: ( a ) Average vHPC-Re coherence spectra from WT ( a i ) and Setd1a +/– ( a ii ) mice during sample, delay, and choice epochs of 10-sec delay trials in Blocked testing in the SWM task. ( b ) FLMM of Genotype and Epoch covariate effects on epoch-level vHPC-Re coherence data during delay (D) relative to sample (S; b i , b iii ) or choice (C; b ii , b iv ) epochs. ( b i , b ii ) Functional coefficient estimates of the Epoch covariate in WT mice, showing differences in the average vHPC-Re coherence at each frequency between epoch types. ( b iii , b iv ) Functional coefficient estimates of the interaction between the Genotype x Epoch covariates, showing how differences in the average vHPC-Re coherence at each frequency between epoch types differ between WT and Setd1a +/– mice. Significant enhancements and reductions (joint CIs do not contain zero) at specific frequencies are denoted by green and red bars, respectively. n=14 WT, 25 Setd1a +/– mice.

Article Snippet: Setd1a tm1a(EUCOMM)Wtsi mice (referred to as Setd1a +/– ) were backcrossed for over 10 generations with C57BL/6J mice (The Jackson Laboratory, Bar Harbor, ME) in the laboratory of J.

Techniques: Functional Assay