CAPRIN1 interacts with Fragile X Mental Retardation Protein (FMRP) at the level of the translation machinery as well as in trafficking neuronal granules (El Fatimay et al., 2012). A de novo nonsense variant in CAPRIN1 was identified in a male ASD proband (Jiang et al., 2013). Pavinato et al., 2022 identified 12 cases with loss-of-function variants in the CAPRIN1 gene presenting with a neurodevelopmental phenotype characterized by language impairment/speech delay (100%), intellectual disability (83%), ADHD (82%), and autism spectrum disorder (67%); patient-derived lymphoblasts and fibroblasts showed monoallelic expression of the wild-type allele and a reduction of the transcript and protein compatible with haploinsufficiency, and studies assessing CAPRIN1-/- human iPSCs generated by CRISPR/Cas9 demonstrated that loss of CAPRIN1 resulted in reduced neuronal processes, overall disruption of neuronal organization, increased neuronal degeneration, altered RNA translation, and impaired calcium signalling and increased oxidative stress.
Molecular Function
May regulate the transport and translation of mRNAs of proteins involved in synaptic plasticity in neurons and cell proliferation and migration in multiple cell types. In neuronal cells, directly binds to several mRNAs associated with RNA granules, including BDNF, CAMK2A, CREB1, MAP2, NTRK2 mRNAs, as well as to GRIN1 and KPNB1 mRNAs, but not to rRNAs .
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Gene-targeting construct was generated from an Caprin1 gene cloned from a 129Sv genomic library; targeted allele contained a deletion of the Caprin1 exon 1;.
Allele Type: Targeted
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6
ES Cell Line: IT2
Mutant ES Cell Line: IT2
Model Source: Tokunaga Laboratory (PMID 20861386)
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Gene-targeting construct was generated from an Caprin1 gene cloned from a 129Sv genomic library; targeted allele contained a deletion of the Caprin1 exon 1;.
Allele Type: Targeted
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6
ES Cell Line: IT2
Mutant ES Cell Line: IT2
Model Source: Tokunaga Laboratory (PMID 20861386)
Description: Caprin1 homozygous null mutant neurons showed a larger decrease in dendritic surface glur1 and quantification revealed that the ratio of surface/total glur1 puncta number in dendrites was significantly reduced in the null mutant neurons compared to wildtype ; ratio of surface/total glur1 appeared to be decreased dose-dependently on caprin1 deficiency, which suggests that even heterozygous knockout of caprin1 impairs the cell surface distribution of ampars
Exp Paradigm: Surface expression of ampar subunit glur1 was detected by immunostaining of live cultured primary neurons from cerebral cortexes of wild-type and caprin1 null mice; caprin1 deficiency reduced the cell surface distribution of ampars in dendrites; dissociated cerebral cortical neurons were prepared at e17.5
Description: Wild-type mice spent a significantly longer time around the cage with a stranger mouse than with a familiar mouse, but the mutant mice spent an equivalent amount of time between the two cages; social interaction with a novel mouse was normal, but that there was a lack of preference for a novel mouse over a familiar mouse in the mutant mice;
Exp Paradigm: In the second session, another unfamiliar mouse (stranger 2) was placed in the cage that had been empty during the first session; the test mouse was then placed in the middle chamber and allowed to explore for 10 min;
Description: Although the social interaction, which was judged by the mean number of particles, of the caprin1+/ mice during the day was comparable to that of the wild-type mice, the social interaction of the caprin1+/ mice was significantly less than wild-type mice during the night; social interaction of familiar mice during an active period was reduced in the caprin1+/ mice;
Exp Paradigm: Home cage behaviorl
Description: For the novel object recogntion task, in the first session, both wild-type and caprin1+/ mice spent similar times around a novel object side and the alternative empty side; in the second session, wild-type mice spent a longer time around a novel object than a familiar object, whereas caprin1+/ mice spent almost the same amount of time between the novel and familiar objects; for the novel place recognition task, wild-type mice showed a reduction in motility on day 2 when they were put into the same combinations of chambers but did not show a reduction in motility on day 2 when they were put into different combinations of chambers ; caprin1+/ mice showed significantly lower motility on day 2 than day 1 in both the same combinations and different combinations
Exp Paradigm: Objects of four types, a black sphere, a black cone, a column with vertical stripes and a cube with black dots, were used in the novel object reginition test; in the novel place regogtition test, mice were put into a novel circle-type or square-type chamber to learn the place pattern on day 1; on day 2, the mice were put into the same chamber (same combination) or another chamber (different combination) to test adaptation for the chamber ; monitored mouse motility, reduction of which suggests adaptation to a place;-object-place recognition test
Description: For the novel object recogntion task, in the first session, both wild-type and caprin1+/ mice spent similar times around a novel object side and the alternative empty side; in the second session, wild-type mice spent a longer time around a novel object than a familiar object, whereas caprin1+/ mice spent almost the same amount of time between the novel and familiar objects; for the novel place recognition task, wild-type mice showed a reduction in motility on day 2 when they were put into the same combinations of chambers but did not show a reduction in motility on day 2 when they were put into different combinations of chambers ; caprin1+/ mice showed significantly lower motility on day 2 than day 1 in both the same combinations and different combinations
Exp Paradigm: Objects of four types, a black sphere, a black cone, a column with vertical stripes and a cube with black dots, were used in the novel object reginition test; in the novel place regogtition test, mice were put into a novel circle-type or square-type chamber to learn the place pattern on day 1; on day 2, the mice were put into the same chamber (same combination) or another chamber (different combination) to test adaptation for the chamber ; monitored mouse motility, reduction of which suggests adaptation to a place;- novel object recognition test
Description: In barnes maze test, no significant differences in the number of errors or distance to first reach the correct hole between wild-type and caprin1+/ mice; caprin1+/ mice showed longer latency than wild-type mice to first reach the correct hole in the reversal learning especially just after the position of the correct hole was changed; in t maze, correct responses to select the rewarded arm and the latency to finish the task were almost the same between mutant and wt; although caprin1+/ mice traveled significantly less distance than wild-type mice to finish the task in the initial training period their travel distance became almost the same as the wild-type mice in the reversal training period
Exp Paradigm: Barnes maze test; t-maze test;-barnes maze test
Description: In barnes maze test, no significant differences in the number of errors or distance to first reach the correct hole between wild-type and caprin1+/ mice; caprin1+/ mice showed longer latency than wild-type mice to first reach the correct hole in the reversal learning especially just after the position of the correct hole was changed; in t maze, correct responses to select the rewarded arm and the latency to finish the task were almost the same between mutant and wt; although caprin1+/ mice traveled significantly less distance than wild-type mice to finish the task in the initial training period their travel distance became almost the same as the wild-type mice in the reversal training period
Exp Paradigm: Barnes maze test; t-maze test;- t-maze test
Description: Caprin1 protein expression levels were reduced to 70-80% in the mutant mice compared to wt; in the brain, spinal nerve, liver and thymus caprin1 protein, but not -tubulin, was reduced;
Exp Paradigm: Western blot;
