Increasing histone acetylation improves sociability and restores learning and memory in KAT6B-haploinsufficient mice
Mutations in genes encoding chromatin modifiers are enriched among mutations causing intellectual disability. The continuing development of the brain postnatally, coupled with the inherent reversibility of chromatin modifications, may afford an opportunity for therapeutic intervention following a ge...
Saved in:
Published in | The Journal of clinical investigation Vol. 134; no. 7; pp. 1 - 20 |
---|---|
Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Clinical Investigation
01.04.2024
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Mutations in genes encoding chromatin modifiers are enriched among mutations causing intellectual disability. The continuing development of the brain postnatally, coupled with the inherent reversibility of chromatin modifications, may afford an opportunity for therapeutic intervention following a genetic diagnosis. Development of treatments requires an understanding of protein function and models of the disease. Here, we provide a mouse model of Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM 603736) and demonstrate proof-of-principle efficacy of postnatal treatment. SBBYSS results from heterozygous mutations in the KAT6B (MYST4/MORF/QFK) gene and is characterized by intellectual disability and autism-like behaviors. Using human cells carrying SBBYSS-specific KAT6B mutations and Kat6b heterozygous mice (Kat6b+/-), we showed that KAT6B deficiency caused a reduction in histone H3 lysine 9 acetylation. Kat6b+/- mice displayed learning, memory, and social deficits, mirroring SBBYSS individuals. Treatment with a histone deacetylase inhibitor, valproic acid, or an acetyl donor, acetyl-carnitine (ALCAR), elevated histone acetylation levels in the human cells with SBBYSS mutations and in brain and blood cells of Kat6b+/- mice and partially reversed gene expression changes in Kat6b+/- cortical neurons. Both compounds improved sociability in Kat6b+/- mice, and ALCAR treatment restored learning and memory. These data suggest that a subset of SBBYSS individuals may benefit from postnatal therapeutic interventions. |
---|---|
AbstractList | Mutations in genes encoding chromatin modifiers are enriched among mutations causing intellectual disability. The continuing development of the brain postnatally, coupled with the inherent reversibility of chromatin modifications, may afford an opportunity for therapeutic intervention following a genetic diagnosis. Development of treatments requires an understanding of protein function and models of the disease. Here, we provide a mouse model of Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM 603736) and demonstrate proof-of-principle efficacy of postnatal treatment. SBBYSS results from heterozygous mutations in the
KAT6B
(
MYST4/MORF/QFK
) gene and is characterized by intellectual disability and autism-like behaviors. Using human cells carrying SBBYSS-specific
KAT6B
mutations and
Kat6b
heterozygous mice (
Kat6b
+/–
), we showed that KAT6B deficiency caused a reduction in histone H3 lysine 9 acetylation.
Kat6b
+/–
mice displayed learning, memory, and social deficits, mirroring SBBYSS individuals. Treatment with a histone deacetylase inhibitor, valproic acid, or an acetyl donor, acetyl-carnitine (ALCAR), elevated histone acetylation levels in the human cells with SBBYSS mutations and in brain and blood cells of
Kat6b
+/–
mice and partially reversed gene expression changes in
Kat6b
+/–
cortical neurons. Both compounds improved sociability in
Kat6b
+/–
mice, and ALCAR treatment restored learning and memory. These data suggest that a subset of SBBYSS individuals may benefit from postnatal therapeutic interventions.
Treatment with a histone deacetylase inhibitor or an acetyl donor shows proof-of-principal efficacy in a mouse model of the cognitive disorder Say-Barber-Biesecker-Young-Simpson syndrome. Mutations in genes encoding chromatin modifiers are enriched among mutations causing intellectual disability. The continuing development of the brain postnatally, coupled with the inherent reversibility of chromatin modifications, may afford an opportunity for therapeutic intervention following a genetic diagnosis. Development of treatments requires an understanding of protein function and models of the disease. Here, we provide a mouse model of Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM 603736) and demonstrate proof-of-principle efficacy of postnatal treatment. SBBYSS results from heterozygous mutations in the KAT6B (MYST4/MORF/QFK) gene and is characterized by intellectual disability and autism-like behaviors. Using human cells carrying SBBYSS-specific KAT6B mutations and Kat6b heterozygous mice (Kat6b+/-), we showed that KAT6B deficiency caused a reduction in histone H3 lysine 9 acetylation. Kat6b+/- mice displayed learning, memory, and social deficits, mirroring SBBYSS individuals. Treatment with a histone deacetylase inhibitor, valproic acid, or an acetyl donor, acetyl-carnitine (ALCAR), elevated histone acetylation levels in the human cells with SBBYSS mutations and in brain and blood cells of Kat6b+/- mice and partially reversed gene expression changes in Kat6b+/- cortical neurons. Both compounds improved sociability in Kat6b+/- mice, and ALCAR treatment restored learning and memory. These data suggest that a subset of SBBYSS individuals may benefit from postnatal therapeutic interventions. Mutations in genes encoding chromatin modifiers are enriched among mutations causing intellectual disability. The continuing development of the brain postnatally, coupled with the inherent reversibility of chromatin modifications, may afford an opportunity for therapeutic intervention following a genetic diagnosis. Development of treatments requires an understanding of protein function and models of the disease. Here, we provide a mouse model of Say-Barber- Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM 603736) and demonstrate proof-of-principle efficacy of postnatal treatment. SBBYSS results from heterozygous mutations in the KAT6B (MYST4/MORF/QFK) gene and is characterized by intellectual disability and autism-like behaviors. Using human cells carrying SBBYSS-specific KAT6B mutations and Kat6b heterozygous mice ([Kat6b.sup.-/-]), we showed that KAT6B deficiency caused a reduction in histone H3 lysine 9 acetylation. Kat6b mice displayed learning, memory, and social deficits, mirroring SBBYSS individuals. Treatment with a histone deacetylase inhibitor, valproic acid, or an acetyl donor, acetyL-carnitine (ALCAR), elevated histone acetylation levels in the human cells with SBBYSS mutations and in brain and blood cells of [Kat6b.sup.-/-] mice and partially reversed gene expression changes in [Kat6b.sup.-/-] cortical neurons. Both compounds improved sociability in Kat6b mice, and ALCAR treatment restored learning and memory. These data suggest that a subset of SBBYSS individuals may benefit from postnatal therapeutic interventions. |
Audience | Academic |
Author | Smyth, Gordon K Thomas, Tim Geoghegan, Niall D Vogel, Adam P Eccles, Samantha Voss, Anne K Vanyai, Hannah K Garnham, Alexandra L Blewitt, Marnie E Hannan, Anthony J Rogers, Kelly L Bergamasco, Maria I |
AuthorAffiliation | 1 The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia 2 Department of Medical Biology and 4 Redenlab Inc., Melbourne, Australia 3 Centre for Neurosciences of Speech, University of Melbourne, Parkville, Victoria, Australia 6 Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia 5 School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria, Australia 7 Department of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, Australia |
AuthorAffiliation_xml | – name: 7 Department of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, Australia – name: 3 Centre for Neurosciences of Speech, University of Melbourne, Parkville, Victoria, Australia – name: 1 The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia – name: 5 School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria, Australia – name: 6 Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia – name: 2 Department of Medical Biology and – name: 4 Redenlab Inc., Melbourne, Australia |
Author_xml | – sequence: 1 givenname: Maria I surname: Bergamasco fullname: Bergamasco, Maria I organization: Department of Medical Biology and – sequence: 2 givenname: Hannah K surname: Vanyai fullname: Vanyai, Hannah K organization: Department of Medical Biology and – sequence: 3 givenname: Alexandra L surname: Garnham fullname: Garnham, Alexandra L organization: Department of Medical Biology and – sequence: 4 givenname: Niall D surname: Geoghegan fullname: Geoghegan, Niall D organization: Department of Medical Biology and – sequence: 5 givenname: Adam P surname: Vogel fullname: Vogel, Adam P organization: Redenlab Inc., Melbourne, Australia – sequence: 6 givenname: Samantha surname: Eccles fullname: Eccles, Samantha organization: Department of Medical Biology and – sequence: 7 givenname: Kelly L surname: Rogers fullname: Rogers, Kelly L organization: Department of Medical Biology and – sequence: 8 givenname: Gordon K surname: Smyth fullname: Smyth, Gordon K organization: School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria, Australia – sequence: 9 givenname: Marnie E surname: Blewitt fullname: Blewitt, Marnie E organization: Department of Medical Biology and – sequence: 10 givenname: Anthony J surname: Hannan fullname: Hannan, Anthony J organization: Department of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, Australia – sequence: 11 givenname: Tim surname: Thomas fullname: Thomas, Tim organization: Department of Medical Biology and – sequence: 12 givenname: Anne K surname: Voss fullname: Voss, Anne K organization: Department of Medical Biology and |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38557491$$D View this record in MEDLINE/PubMed |
BookMark | eNqNkt-L1DAQx4uceD_0wX9AAoLoQ8-kSZv2SdbFH6sHB3r6GtJ00s2RJmvSHu5_b4rnuiv7IIEkzHzmO5nMnGcnzjvIsqcEXxLCi9eflitS8YoXD7IzUpZ1Xhe0Ptm7n2bnMd5iTBgr2aPslNZlyVlDzrJx5VQAGY3r0drEMQkjqWDcWjka75AZNsHfQUTRKyNbY824RdJ1KECC04YsyODm8Nk6wODDFhmHPi9uqrf5Wm6sNy5OWhtlwI1oMAoeZw-1tBGe3J8X2bf3726WH_Or6w-r5eIqV6ypx1xxWXa8bpuyLZjuNC_KVGPLaNfISnWzQ5IOWioLyssaV4poBjiFaKrrjtCL7M1v3c3UDtCplD9IKzbBDDJshZdGHHqcWYve3wmCG86bmiaFl_cKwf-YUsliMFGBtdKBn6KgmBJCeVVXCX3-D3rrp-BSfTPFcUMJZX-pXloQxmmfEqtZVCx4Q3BZMMwTlR-henCQXplapE0yH_CXR_i0Okj_fTTg1UFAYkb4OfZyilGsvn75f_b6-yH7Yo9dg7TjOno7zbMUj4qq4GMMoHddIVjMQy12Q53YZ_tt3JF_ppj-AguP8TE |
Cites_doi | 10.1128/MCB.00159-10 10.1073/pnas.1216100110 10.1093/nar/23.24.5080 10.1016/j.bbr.2016.10.012 10.1111/j.1471-4159.1981.tb00569.x 10.1203/01.PDR.0000028406.01104.76 10.1111/j.1528-1167.2006.00711.x 10.1038/ejhg.2014.248 10.1038/s41436-020-0811-8 10.1038/43487 10.1016/j.biopsych.2009.11.008 10.1016/j.neulet.2009.12.054 10.1038/nrd2681 10.1016/j.chembiol.2023.07.005 10.1111/j.1399-5618.2007.00481.x 10.1016/j.neulet.2021.136241 10.1016/j.ajhg.2011.10.008 10.1016/j.brainres.2021.147670 10.1128/MCB.00506-19 10.2741/4459 10.1371/journal.pone.0051586 10.1016/j.pbb.2014.08.013 10.12659/MSM.881792 10.1016/j.neuroscience.2009.11.073 10.1016/S0387-7604(01)00346-1 10.1016/j.neuint.2012.04.008 10.1111/j.1471-4159.2010.06807.x 10.1016/j.neuroscience.2019.02.022 10.1158/0008-5472.CAN-17-1388 10.1016/j.pneurobio.2013.04.001 10.1016/j.ajhg.2011.11.023 10.1523/JNEUROSCI.2247-06.2006 10.1016/j.devcel.2009.10.023 10.1016/j.neuroscience.2010.06.069 10.1038/376348a0 10.1111/j.1399-0004.2008.01087.x 10.1002/humu.22141 10.1038/s41467-019-12551-5 10.1002/mgg3.2202 10.1371/journal.pone.0048975 10.1523/JNEUROSCI.23-07-03001.2003 10.1242/jcs.077271 10.1016/j.neuroscience.2014.11.025 10.1126/scitranslmed.aad9407 10.1242/dev.127.12.2537 10.1016/j.jalz.2016.09.003 10.1016/j.yebeh.2017.02.026 10.3389/fnagi.2018.00137 10.1523/JNEUROSCI.0110-07.2007 10.1158/0008-5472.CAN-04-3011 10.1111/j.1528-1167.2007.01323.x 10.1016/j.neuron.2004.05.021 10.1158/0008-5472.CAN-14-3702 10.1038/sj.onc.1205367 10.1038/35089085 10.1172/JCI43428 10.1126/scitranslmed.3009278 10.1016/j.molcel.2005.12.007 10.1016/j.ajhg.2018.06.009 |
ContentType | Journal Article |
Copyright | COPYRIGHT 2024 American Society for Clinical Investigation Copyright American Society for Clinical Investigation Apr 2024 2024 Bergamasco et al. 2024 Bergamasco et al. |
Copyright_xml | – notice: COPYRIGHT 2024 American Society for Clinical Investigation – notice: Copyright American Society for Clinical Investigation Apr 2024 – notice: 2024 Bergamasco et al. 2024 Bergamasco et al. |
DBID | NPM AAYXX CITATION IOV ISR 3V. 7RV 7X7 7XB 88A 88E 8AO 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BEC BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ HCIFZ K9. KB0 LK8 M0S M1P M7P NAPCQ PQEST PQQKQ PQUKI S0X 7X8 5PM |
DOI | 10.1172/JCI167672 |
DatabaseName | PubMed CrossRef Gale In Context: Opposing Viewpoints Gale In Context: Science ProQuest Central (Corporate) Nursing & Allied Health Database Health & Medical Collection ProQuest Central (purchase pre-March 2016) Biology Database (Alumni Edition) Medical Database (Alumni Edition) ProQuest Pharma Collection ProQuest SciTech Collection ProQuest Natural Science Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central ProQuest Central Essentials Biological Science Collection eLibrary ProQuest Central Natural Science Collection ProQuest One Community College ProQuest Central Korea Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Database (Alumni Edition) Biological Sciences Health & Medical Collection (Alumni Edition) PML(ProQuest Medical Library) Biological Science Database Nursing & Allied Health Premium ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic ProQuest One Academic UKI Edition SIRS Editorial MEDLINE - Academic PubMed Central (Full Participant titles) |
DatabaseTitle | PubMed CrossRef ProQuest Central Student ProQuest Central Essentials SIRS Editorial elibrary ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Biology Journals (Alumni Edition) ProQuest Central Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Biological Science Collection ProQuest Medical Library (Alumni) ProQuest Biological Science Collection ProQuest One Academic Eastern Edition ProQuest Nursing & Allied Health Source ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection ProQuest Hospital Collection (Alumni) Nursing & Allied Health Premium ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest Nursing & Allied Health Source (Alumni) ProQuest One Academic ProQuest Central (Alumni) MEDLINE - Academic |
DatabaseTitleList | ProQuest Central Student PubMed MEDLINE - Academic |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1558-8238 |
EndPage | 20 |
ExternalDocumentID | A791052407 10_1172_JCI167672 38557491 |
Genre | Journal Article |
GeographicLocations | Australia |
GeographicLocations_xml | – name: Australia |
GrantInformation_xml | – fundername: Australian Government grantid: Independent Research Institutes Infrastructure Support Scheme – fundername: Victorian Government grantid: Operational Infrastructure Support Grant – fundername: Australian National Health and Medical Research Council grantid: 1160517,2010711,1081421,1176789,1194345,1154970 |
GroupedDBID | --- -~X .55 .XZ 08G 08P 29K 354 36B 3V. 5GY 5RE 5RS 7RV 7X7 88A 88E 8AO 8F7 8FE 8FH 8FI 8FJ 8R4 8R5 AAWTL ABOCM ABPMR ABUWG ACGFO ACIHN ACNCT ACPRK ADBBV AEAQA AENEX AFCHL AFKRA AHMBA ALIPV ALMA_UNASSIGNED_HOLDINGS AOIJS ASPBG AVWKF AZFZN BAWUL BBNVY BCU BEC BENPR BHPHI BKEYQ BLC BPHCQ BVXVI CCPQU CS3 D-I DIK DU5 E3Z EBS EJD EMB EX3 F5P FRP FYUFA GROUPED_DOAJ GX1 HCIFZ HMCUK IAO IEA IHR IHW INH INR IOF IOV IPO ISR ITC KQ8 L7B LK8 M0L M1P M5~ M7P NAPCQ NPM OBH OCB ODZKP OFXIZ OGEVE OHH OK1 OVD OVIDX P2P P6G PQQKQ PROAC PSQYO Q2X RPM S0X SJFOW SV3 TEORI TR2 TVE UKHRP VVN W2D WH7 WOQ WOW X7M XSB YFH YHG YKV YOC ZY1 ~H1 AAYXX CITATION 7XB 8FK AZQEC DWQXO GNUQQ K9. PQEST PQUKI 7X8 5PM |
ID | FETCH-LOGICAL-c498t-c7a5d78b95b24fdf725672b43d9a6cd8b95a1deb3a2375806c1f4e0d78f3f8d13 |
IEDL.DBID | 7X7 |
ISSN | 1558-8238 0021-9738 |
IngestDate | Tue Sep 17 21:29:11 EDT 2024 Sat Oct 26 05:41:16 EDT 2024 Thu Nov 21 03:18:21 EST 2024 Tue Nov 19 21:35:54 EST 2024 Thu Nov 14 21:29:34 EST 2024 Tue Nov 12 23:48:51 EST 2024 Sat Sep 28 21:23:07 EDT 2024 Sat Sep 28 21:13:40 EDT 2024 Tue Aug 20 22:16:10 EDT 2024 Fri Dec 06 03:06:14 EST 2024 Sat Nov 02 12:22:42 EDT 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 7 |
Keywords | Development Epigenetics Neurodevelopment Genetics Genetic diseases |
Language | English |
License | http://creativecommons.org/licenses/by/4.0 This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c498t-c7a5d78b95b24fdf725672b43d9a6cd8b95a1deb3a2375806c1f4e0d78f3f8d13 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Authorship note: TT and AKV are co–senior authors. |
ORCID | 0000-0002-7623-8344 0000-0001-9221-2892 0000-0002-3505-2631 0000-0003-3322-9701 0000-0002-8312-8450 |
OpenAccessLink | http://dx.doi.org/10.1172/JCI167672 |
PMID | 38557491 |
PQID | 3037093134 |
PQPubID | 42166 |
PageCount | 20 |
ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_10977983 proquest_miscellaneous_3031137686 proquest_journals_3037093134 gale_infotracmisc_A791052407 gale_infotracgeneralonefile_A791052407 gale_infotracacademiconefile_A791052407 gale_incontextgauss_ISR_A791052407 gale_incontextgauss_IOV_A791052407 gale_healthsolutions_A791052407 crossref_primary_10_1172_JCI167672 pubmed_primary_38557491 |
PublicationCentury | 2000 |
PublicationDate | 2024-Apr-01 2024-4-1 20240401 |
PublicationDateYYYYMMDD | 2024-04-01 |
PublicationDate_xml | – month: 04 year: 2024 text: 2024-Apr-01 day: 01 |
PublicationDecade | 2020 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States – name: Ann Arbor |
PublicationTitle | The Journal of clinical investigation |
PublicationTitleAlternate | J Clin Invest |
PublicationYear | 2024 |
Publisher | American Society for Clinical Investigation |
Publisher_xml | – name: American Society for Clinical Investigation |
References | B20 B21 B22 B23 B24 B25 B26 B27 B28 B29 B30 B31 B32 B33 B34 B35 B36 B37 B38 B39 B1 B2 B3 B4 B5 B6 B7 B8 B9 Kelley (B15) 2019; 179 B40 B41 B42 B43 B44 B45 B46 B47 B48 B49 B50 B51 B52 B53 B10 B54 B11 B55 B12 B56 B13 B57 B14 B58 B59 B16 B17 B18 B19 B60 B61 |
References_xml | – ident: B30 doi: 10.1128/MCB.00159-10 – ident: B48 doi: 10.1073/pnas.1216100110 – ident: B61 doi: 10.1093/nar/23.24.5080 – ident: B40 doi: 10.1016/j.bbr.2016.10.012 – ident: B50 doi: 10.1111/j.1471-4159.1981.tb00569.x – ident: B41 doi: 10.1203/01.PDR.0000028406.01104.76 – ident: B23 doi: 10.1111/j.1528-1167.2006.00711.x – ident: B16 doi: 10.1038/ejhg.2014.248 – ident: B3 doi: 10.1038/s41436-020-0811-8 – ident: B10 doi: 10.1038/43487 – ident: B37 doi: 10.1016/j.biopsych.2009.11.008 – ident: B42 doi: 10.1016/j.neulet.2009.12.054 – ident: B18 doi: 10.1038/nrd2681 – ident: B29 doi: 10.1016/j.chembiol.2023.07.005 – ident: B38 doi: 10.1111/j.1399-5618.2007.00481.x – ident: B55 doi: 10.1016/j.neulet.2021.136241 – ident: B1 doi: 10.1016/j.ajhg.2011.10.008 – ident: B60 doi: 10.1016/j.brainres.2021.147670 – ident: B31 doi: 10.1128/MCB.00506-19 – ident: B24 – ident: B25 doi: 10.2741/4459 – ident: B46 doi: 10.1371/journal.pone.0051586 – ident: B34 doi: 10.1016/j.pbb.2014.08.013 – ident: B44 doi: 10.12659/MSM.881792 – ident: B35 doi: 10.1016/j.neuroscience.2009.11.073 – ident: B45 doi: 10.1016/S0387-7604(01)00346-1 – ident: B49 doi: 10.1016/j.neuint.2012.04.008 – ident: B52 doi: 10.1111/j.1471-4159.2010.06807.x – volume: 179 start-page: 729 issue: 4 year: 2019 ident: B15 article-title: KAT6A syndrome: deficiency of a histone acetyltransferase as the cause of mild to severe mitochondrial disease publication-title: Am J Med Genet contributor: fullname: Kelley – ident: B36 doi: 10.1016/j.neuroscience.2019.02.022 – ident: B28 doi: 10.1158/0008-5472.CAN-17-1388 – ident: B19 doi: 10.1016/j.pneurobio.2013.04.001 – ident: B2 doi: 10.1016/j.ajhg.2011.11.023 – ident: B8 doi: 10.1523/JNEUROSCI.2247-06.2006 – ident: B58 doi: 10.1016/j.devcel.2009.10.023 – ident: B20 doi: 10.1016/j.neuroscience.2010.06.069 – ident: B57 doi: 10.1038/376348a0 – ident: B17 doi: 10.1111/j.1399-0004.2008.01087.x – ident: B4 doi: 10.1002/humu.22141 – ident: B12 doi: 10.1038/s41467-019-12551-5 – ident: B26 doi: 10.1002/mgg3.2202 – ident: B43 doi: 10.1371/journal.pone.0048975 – ident: B51 doi: 10.1523/JNEUROSCI.23-07-03001.2003 – ident: B7 doi: 10.1242/jcs.077271 – ident: B47 doi: 10.1016/j.neuroscience.2014.11.025 – ident: B54 doi: 10.1126/scitranslmed.aad9407 – ident: B6 doi: 10.1242/dev.127.12.2537 – ident: B14 doi: 10.1016/j.jalz.2016.09.003 – ident: B22 doi: 10.1016/j.yebeh.2017.02.026 – ident: B53 doi: 10.3389/fnagi.2018.00137 – ident: B33 doi: 10.1523/JNEUROSCI.0110-07.2007 – ident: B21 doi: 10.1158/0008-5472.CAN-04-3011 – ident: B39 doi: 10.1111/j.1528-1167.2007.01323.x – ident: B59 doi: 10.1016/j.neuron.2004.05.021 – ident: B11 doi: 10.1158/0008-5472.CAN-14-3702 – ident: B32 doi: 10.1038/sj.onc.1205367 – ident: B9 doi: 10.1038/35089085 – ident: B27 doi: 10.1172/JCI43428 – ident: B56 doi: 10.1126/scitranslmed.3009278 – ident: B13 doi: 10.1016/j.molcel.2005.12.007 – ident: B5 doi: 10.1016/j.ajhg.2018.06.009 |
SSID | ssj0014454 |
Score | 2.511011 |
Snippet | Mutations in genes encoding chromatin modifiers are enriched among mutations causing intellectual disability. The continuing development of the brain... |
SourceID | pubmedcentral proquest gale crossref pubmed |
SourceType | Open Access Repository Aggregation Database Index Database |
StartPage | 1 |
SubjectTerms | Acetylation Alzheimer's disease Analysis Animal models Autism Blood cells Brain Care and treatment Carnitine Cells Chromatin CRISPR Diagnosis Divalproex Fetuses Gene expression Genetic aspects Genetic screening Health aspects Histone deacetylase Histone H3 Histones Intellectual disabilities Mental retardation Mice Morphology Mutation Phenotype Proteins Social discrimination learning Therapeutic applications Valproic acid Weaning |
Title | Increasing histone acetylation improves sociability and restores learning and memory in KAT6B-haploinsufficient mice |
URI | https://www.ncbi.nlm.nih.gov/pubmed/38557491 https://www.proquest.com/docview/3037093134 https://search.proquest.com/docview/3031137686 https://pubmed.ncbi.nlm.nih.gov/PMC10977983 |
Volume | 134 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3fb9MwELZgkxAviN8LjGIQgqdocezEzhPqpk3b0AYaG-pb5J9dJUjLmj70v-fsuGFBCPFaf6kS3_nO53z5DqF3mRJSkNKlmYEQyJRzqbQmS4VkrDBMVjZwc87Oy-MrdjopJvHAbRlplZuYGAK1mWt_Rr4HoZZD9U0o-7j4mfquUf7tamyhcRdtkxxSOfgzn_QFF9QKRVRhJmnFqYjKQpCz904PTojXKssH-ejPqHwrLQ0pk7dy0NFD9CBuHvG4s_YjdMc2j9G9s_h6_AlqYbV7kjmkIxyEhBuLpbbtuiO84Vk4QbBLHEwSaLFrLBuDb0J_GRiITSSm4dcfnoW7xrMGfxpflvvptVx8n3vyepCdgFvEvpf9U3R1dHh5cJzGtgqpZpVoU81lYbhQVaFy5ozjsOvhuWLUVLLUxg9IYqDIljmFaiIrNXHMZnCJo04YQp-hrQYeYAdhwyyU0NQYBRCwOBg-I0prRZWlTosEvd1Mbr3o1DPqUHXwvO4tkKDXftrr7sPPfsXVYw5bmcJXnPA3AeH1KhpPiJnK1XJZn3z-9h-grxcD0IcIcnOwo5bxIwR4HK-DNUC-HyCnnQr434C7AyAsTz0c3nhTHcPDsv7tzAl60w_7Kz3lrbHzVcAQAuFflAl63jlfP4dUFAVnFUmQGLhlD_Ci4cORZnYdxMM944BXgr749329RPdz2L51HKVdtNXerOwr2H61ahTW2Aht7x-ef7kYhUOMX1YOM3I |
link.rule.ids | 230,314,780,784,864,885,12056,21388,27924,27925,31719,31720,33744,33745,43310,43805,73745,74302 |
linkProvider | ProQuest |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3Pb9MwFLagk4AL4ucIDGYQglO0OHZi54S6aVO7rQWNDu0WObbTVYK0LOmh_z3PjhsWhBDX-kua-Nnv-dlfvofQ-6gQUpC0DCMNLpAVZRlKo6NQSMYSzWRmHDdnMk1Hl-z0KrnyG261p1VufaJz1Hqp7B75AbhaDtk3oezT6mdoq0bZ01VfQuMu2rHK6ckA7RweT79cdOcI8Ideh5mEGafCawtB1D44PRoTq1YW9yLSn375VmDqkyZvRaGTR-ihXz7iYWvvx-iOqZ6gexN_QP4UNTDfLc0cAhJ2UsKVwVKZZtNS3vDC7SGYGjujOGLsBstK4xtXYQYafBmJufv1h-XhbvCiwmfDWXoYXsvV96WlrzvhCXhEbKvZP0OXJ8ezo1HoCyuEimWiCRWXieaiyJIiZqUuOax7eFwwqjOZKm0bJNGQZsuYQj4RpYqUzERwSUlLoQl9jgYVvMALhDUzkERTrQuAgM3B9BEplCpoYWipRIDebTs3X7X6GbnLO3icdxYI0L7t9rz99LObc_mQw2ImsTkn3MYhrGJFZSkxc7mu63z8-dt_gL5e9EAfPahcgh2V9J8hwOtYJawe8kMPOW91wP8G3OsBYYKqfvN2NOXeQdT57-EcoLdds73Skt4qs1w7DCEQAEQaoN128HV9SEWScJaRAInesOwAVja831Itrp18uOUc8EzQl_9-rn10fzSbnOfn4-nZK_QghsVcy1jaQ4PmZm1ew2KsKd74GfcLNwA1OQ |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1bb9MwFLagkyZeEHcyBjMIwVPUOHYS5wl1Y9W6sTKNDe0tcnzpKkHaLelD_z3HjhsWhBCv8ZebfXyOT_zlOwi9j0ouOElNGClwgaw0JhRaRSEXjCWKiVw7bs7pND26ZMdXyZXnP9WeVrnxic5Rq4W038iH4GozyL4JZUPjaRFnn8efljehrSBld1p9OY37aAuiYhQP0Nb-4fTsvNtTgJt7TWYS5hnlXmcIIvjw-GBCrHJZ3ItOf_roO0GqT6C8E5HGj9BDv5TEo3bsH6N7unqCtk_9ZvlT1MDct5RzCE7YyQpXGgupm3VLf8Nz9z1B19gNkCPJrrGoFL511WagwZeUmLmjPy0nd43nFT4ZXaT74bVY_lhYKrsToYBHxLay_TN0OT68ODgKfZGFULKcN6HMRKIyXuZJGTOjTAZroCwuGVW5SKWyDYIoSLlFTCG3iFJJDNMRnGKo4YrQ52hQwQu8RFgxDQk1VaoECIw_mEFESilLWmpqJA_Qu03nFstWS6NwOUgWF90IBGjPdnvR_gbazb9ilMHCJrH5J1zGIax6RWXtYCZWdV1Mvn7_D9C38x7ooweZBYyjFP6XBHgdq4rVQ37oIWetJvjfgLs9IExW2W_eWFPhnUVd_DbtAL3tmu2ZlgBX6cXKYQiBYMDTAL1oja_rQ8qTJGM5CRDvmWUHsBLi_ZZqfu2kxC3_IMs53fn3c-2hbZhsxZfJ9OQVehDDuq4lL-2iQXO70q9hXdaUb_yE-wWk0jlm |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Increasing+histone+acetylation+improves+sociability+and+restores+learning+and+memory+in+KAT6B-haploinsufficient+mice&rft.jtitle=The+Journal+of+clinical+investigation&rft.au=Bergamasco%2C+Maria+I&rft.au=Vanyai%2C+Hannah+K&rft.au=Garnham%2C+Alexandra+L&rft.au=Geoghegan%2C+Niall+D&rft.date=2024-04-01&rft.pub=American+Society+for+Clinical+Investigation&rft.issn=0021-9738&rft.volume=134&rft.issue=7&rft_id=info:doi/10.1172%2FJCI167672&rft.externalDocID=A791052407 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1558-8238&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1558-8238&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1558-8238&client=summon |