This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014).
Molecular Function
This gene encodes a multi-domain protein that is predominantly expressed in brain and testis. This protein interacts with amyloid beta protein precursor (AbetaPP) and may have a role in normal brain development, and in the pathogenesis of Alzheimer's disease.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.
Anks1b happloinsufficient mice show social deficits, hyperactivity, decrease in anxiety, and sensorimotor dysfunction. Anks1b happloinsufficient mice show sex-specific differences, with a decrease in weight, body length, and brain mass in male mice that was not significant in females. Anks1b happloinsufficient mice show no histological changes in the hippocampus and cerebellum, no change in grooming, no change in homing, negative geotaxis, and acoustic startle tests in pups from P10 to P16. Mutants show no developmental delay. Mutants show no change in frequency, syllable counts and intervals, or syllable repertoires in ultrasonic vocalization.
References
Type
Title
Author, Year
Primary
Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
A transgenic Nestin-Cre mouse line deletes exon 7 of Anks1B, the first exon of the phosphotyrosine binding domain (PTB) flanked by loxp sites, from the developing central and peripheral nervous system starting at embryonic day 11. Nestin-Cre;Anks1b^wt/wt littermates (Nestin-WT mice) are used as controls.
Allele Type: Conditional knockout
Strain of Origin: Genetic Background: C57BL/6J
ES Cell Line: Mutant ES Cell Line: Model Source: Tindi JO, et al, 2015 (Anks1B-floxed); Jackson Laboratories (Nestin-Cre, #003771)
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A transgenic Nestin-Cre mouse line deletes exon 7 of Anks1B, the first exon of the phosphotyrosine binding domain (PTB) flanked by loxp sites, from the developing central and peripheral nervous system starting at embryonic day 11. Nestin-Cre;Anks1b^wt/wt littermates (Nestin-WT mice) are used as controls.
Allele Type: Conditional knockout
Strain of Origin: Genetic Background: C57BL/6J
ES Cell Line: Mutant ES Cell Line: Model Source: Tindi JO, et al, 2015 (Anks1B-floxed); Jackson Laboratories (Nestin-Cre, #003771)
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Olig2-heterozygote mice have one copy of the Anks1b-flox allele (MGI:5779292) in which exon 20 is flanked by loxP sites, and one copy of the Olig2-Cre gene (MGI:3810299) which encodes the transgene with the avian specific retroviral receptor (TVA) followed by an IRES-cre and neo cassette inserted immediately downstream of the Olig2 translation initiation site.
Allele Type: Conditional knockout
Strain of Origin: (C57BL/6NTac x 129S6/SvEvTac)F1; 129
Genetic Background: C57BL/6J
ES Cell Line: iTL BA1; Not specified
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Olig2-knockout mice have two copies of the Anks1b-flox allele (MGI:5779292) in which exon 20 is flanked by loxP sites, and one copy of the Olig2-Cre gene (MGI:3810299) which encodes the transgene with the avian specific retroviral receptor (TVA) followed by an IRES-cre and neo cassette inserted immediately downstream of the Olig2 translation initiation site.
Allele Type: Conditional knockout
Strain of Origin: (C57BL/6NTac x 129S6/SvEvTac)F1; 129
Genetic Background: C57BL/6J
ES Cell Line: iTL BA1; Not specified
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
L7-heterozygote mice have one copy of the Anks1b-flox allele (MGI:5779292) in which exon 20 is flanked by loxP sites, and one copy of the L7-Cre transgene (MGI:2137515) which encodes the Cre recombinase under the direction of the Purkinje cell-specific L7/Pcp2 promoter.
Allele Type: Conditional knockout
Strain of Origin: (C57BL/6NTac x 129S6/SvEvTac)F1; (129X1/SvJ x 129S
Genetic Background: Not specified
ES Cell Line: iTL BA1; R1
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
L7-knockout mice have two copies of the Anks1b-flox allele (MGI:5779292) in which exon 20 is flanked by loxP sites, and one copy of the L7-Cre transgene (MGI:2137515) which encodes the Cre recombinase under the direction of the Purkinje cell-specific L7/Pcp2 promoter.
Allele Type: Conditional knockout
Strain of Origin: (C57BL/6NTac x 129S6/SvEvTac)F1; (129X1/SvJ x 129S
Genetic Background: Not specified
ES Cell Line: iTL BA1; R1
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
CamK2a-knockout mice have two copies of the Anks1b-flox allele (MGI:5779292) in which exon 20 is flanked by loxP sites, and one copy of the CamK2a-Cre transgene (MGI:2177650) which encodes Cre recombinase under the control of the alpha subunit of the calcium/calmodulin-dependent protein kinase II promoter.
Allele Type: Conditional knockout
Strain of Origin: (C57BL/6NTac x 129S6/SvEvTac)F1; Not specified
Genetic Background: Not specified
ES Cell Line: iTL BA1; Not specified
Mutant ES Cell Line: Model Source:
Description: Nestin-heterozygote mice show a decrease in immunostaining for myelin basic protein (MBP) in the corpus callosum and cerebellar cortex.
Exp Paradigm: Myelin basic protein
Description: Nestin-heterozygous mice show a significant decrease in the volume of the corpus callosum.
Exp Paradigm: T2-weighted MRIs of ex vivo brain tissue from 10 female Anks1b Nestin-Het and 10 female WT controls (age 3 months) reveal
Description: In Nestin-heterozygote mice, there are significantly fewer mature oligodendrocytes (CC1-positive) derived from newborn cells throughout all time points tested. There is also a significant increase in OPCs and immature oligodendrocytes (PDGFRa- positive) in Nestin-heterozygote mice at 3 weeks and 6 months of age.
Exp Paradigm: CC1, PDGFRa
Description: Brain slices stained with Luxol Fast Blue (LFB), a copper phthalocyanine dye that binds to lipoproteins of the myelin sheath, show that both male and female Nestin-heterozygote mice have decreased LFB staining intensity compared to wildtype littermates in the corpus callosum as well as in the cerebellum.
Exp Paradigm: Luxol Fast Blue
Description: Newborn oligodendrocytes accumulated at lesioned areas in wildtype mice, and then dispersed throughout the corpus callosum. In contrast, there are significantly fewer newborn cells in demyelinated areas in Nestin-heterozygote mice. Moreover, significantly fewer of these cells were of oligodendrocyte lineage, as indicated by co-labeling with Olig2.
Exp Paradigm: after injury in corpus callosum
DTI: fractional anisotropy or relative anisotropy in brain regions2
Decreased
Description: In vivo DTI analyses of Nestin-heterozygote mouse brains show a significant decrease in fractional anisotropy of callosal and other tracts.
Exp Paradigm: T2-weighted MRIs of ex vivo brain tissue from 10 female Anks1b Nestin-Het and 10 female WT controls (age 3 months) reveal
Description: Quantification revealed a significant increase in g-ratio (signifying decreased myelination) in Nestin-heterozygote mice in the most common axon diameters (0.3â??1.7 microns).
g-ratio measurement (axon diameters/fiber diameters of myelinated axons)
Description: Nissl staining confirmed that Nestin-heterozygote mice have a thinner corpus callosum throughout the rostrocaudal axis.
Exp Paradigm: Nissl
Description: Olig2-heterozygote mice show significantly increased sensory hyperreactivity as demonstrated by increased startle to sounds at 100 dB and 110 dB, but not at 90 dB compared to wildtype littermates.
Description: Olig2-heterozygote mice spent more time in the open arms of the elevated plus maze (decreased anxiety) but covered less distance in the open arms (increased anxiety).
Description: Olig2-knockout mice show significantly increased sensory hyperreactivity as demonstrated by increased startle to sounds at 100 dB and 110 dB, but not at 90 dB compared to wildtype littermates.
Description: Oligodendrocyte-specific Anks1b homozygous (Olig2-knockout) mice are viable, although knockout mice were born at rates below expected Mendelian ratios and were smaller than their wildtype counterparts.
Genotypic ratio of progeny from heterozygous parents
Description: Olig2-knockout mice spent more time in the open arms of the elevated plus maze (decreased anxiety) but covered less distance in the open arms (increased anxiety).
