Heterozygous mice with Ric-8 mutation exhibit impaired spatial memory and decreased anxiety

Tõnissoo, Tambet; Kõks, Sulev; Meier, Riho; Raud, Sirli; Plaas, Mario; Vasar, Eero; Karis, Alar

doi:10.1016/j.bbr.2005.08.025

Cited by 26 publications

(35 citation statements)

References 15 publications

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“…At that stage, the expression of RIC-8 was also expressed in extra-embryonic tissues, such as parietal and visceral endoderm, extra-embryonic ectoderm and mesoderm, hematocytoblasts, allantois, and amnion ( Fig. 1E and F their wild type littermates and had no evident morphological or anatomical deviations, and they were fertile as shown earlier (Tõnissoo et al, 2006). However, no Ric-8 À/À mutants were recovered in 120 newborn animals, whereas both the wild type Ric-8 þ/þ and heterozygous Ric-8 þ/À offsprings were obtained, suggesting that the homozygous mutation leads to embryonic lethality (Table 1).…”

Section: Expression Of Ric-8 During Early Embryogenesis Of Mousesupporting

confidence: 73%

“…The construction of Ric-8 targeting vectors and generation of chimeric mice were carried through as described earlier (Tõnissoo et al, 2006). In the present study, C57Bl/6J mice were used as wild type strain and heterozygous Ric-8 þ/À backcrosses were used to obtain Ric-8 À/À mutant animals.…”

Section: Methodsmentioning

confidence: 99%

“…In order to characterize the function of the nucleotide exchange factor RIC-8 in the mammalian development at earlier stages, we used mice with a mutant Ric-8 gene (Tõnissoo et al, 2006). We mapped the maldevelopment of RIC-8 mutant embryos and demonstrate here that the embryos lacking RIC-8 were able to implant and to initiate gastrulation.…”

Section: Introductionmentioning

confidence: 99%

“…In comparison, the murine RIC-8 potentiates the Gq-mediated signal transduction in intact cells by using a novel mechanism in G-protein regulation in vertebrates (Nishimura et al, 2006). In adult mice, RIC-8 is expressed in the brain regions involved in the regulation of behavior, e.g., neocortex, cingulated cortex, corpus striatum, hippocampus, cerebellum, and pineal gland (Tõnissoo et al, 2003(Tõnissoo et al, , 2006. The insufficiency of RIC-8 in heterozygous mice leads to increased anxiety and causes problems with spatial memory and relearning, suggesting that it has an important role in the regulation of memory and emotional behavior (Tõnissoo et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…In adult mice, RIC-8 is expressed in the brain regions involved in the regulation of behavior, e.g., neocortex, cingulated cortex, corpus striatum, hippocampus, cerebellum, and pineal gland (Tõnissoo et al, 2003(Tõnissoo et al, , 2006. The insufficiency of RIC-8 in heterozygous mice leads to increased anxiety and causes problems with spatial memory and relearning, suggesting that it has an important role in the regulation of memory and emotional behavior (Tõnissoo et al, 2006). In addition, it was shown recently that RIC-8 is expressed in a large proportion of mouse taste bud cells where it potentiates taste receptor signaling (Fenech et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Tõnissoo¹,

Lulla²,

Meier³

et al. 2010

Developmental Dynamics

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The guanine nucleotide exchange factor RIC-8 is a conserved protein essential for the asymmetric division in the early embryogenesis in different organisms. The function of RIC-8 in mammalian development is not characterized so far. In this study we map the expression of RIC-8 during the early development of mouse. To elucidate the RIC-8 function we used Ric-8 2/2 mutant embryos. The Ric-8 2/2 embryos reach the gastrulation stage but do not develop further and die at E6.5-E8.5. We characterized the Ric-8 2/2 embryonic phenotype by morphological and marker gene analyses. The gastrulation is initiated in Ric-8 2/2 embryos but their growth is retarded, epiblast and mesoderm disorganized. Additionally, the basement membrane is defective, amnion folding and the formation of allantois are interfered, also the cavitation. Furthermore, the orientation of the Ric-8 2/2 embryo in the uterus was abnormal. Our study reveals that the activity of RIC-8 protein is irreplaceable for the correct gastrulation of mouse embryo. Developmental Dynamics 239:3404-3415,

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Section: Expression Of Ric-8 During Early Embryogenesis Of Mousesupporting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Tõnissoo¹,

Lulla²,

Meier³

et al. 2010

Developmental Dynamics

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Activators of G ‐Protein Signaling in the Normal and Diseased Kidney

Park

2022

GPCRs as Therapeutic Targets

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Deletion of RIC8A in neural precursor cells leads to altered neurogenesis and neonatal lethality of mouse

Kask

Ruisu

Tikker

et al. 2015

Developmental Neurobiology

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RIC8A is a noncanonical guanine nucleotide exchange factor for a subset of Gα subunits. RIC8A has been reported in different model organisms to participate in the control of mitotic cell division, cell signalling, development and cell migration. Still, the function of RIC8A in the mammalian nervous system has not been sufficiently analysed yet. Adult mice express RIC8A in the brain regions involved in the regulation of memory and emotional behaviour. To elucidate the role of RIC8A in mammalian neurogenesis we have inactivated Ric8a in neural precursor cells using Cre/Lox system. As a result, the conditional knockout mice were born at expected Mendelian ratio, but died or were cannibalized by their mother within 12 h after birth. The cerebral cortex of the newborn Nes;Ric8a(CKO) mice was thinner compared to littermates and the basement membrane was discontinuous, enabling migrating neurons to invade to the marginal zone. In addition, the balance between the planar and oblique cell divisions was altered, influencing the neuron production. Taken together, RIC8A has an essential role in the development of mammalian nervous system by maintaining the integrity of pial basement membrane and modulating cell division.

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Heterozygous mice with Ric-8 mutation exhibit impaired spatial memory and decreased anxiety

Cited by 26 publications

References 15 publications

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Activators of G ‐Protein Signaling in the Normal and Diseased Kidney

Deletion of RIC8A in neural precursor cells leads to altered neurogenesis and neonatal lethality of mouse

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