Alteration of behavioural phenotype in mice by targeted disruption of the progranulin gene

Kayasuga, Yuko; Chiba, Shuichi; Suzuki, Masatoshi; Kikusui, Takefumi; Matsuwaki, Takashi; Yamanouchi, Keitaro; Kotaki, Hayato; Horai, Reiko; Iwakura, Yoichiro; Nishihara, Masugi

doi:10.1016/j.bbr.2007.07.020

Cited by 176 publications

(187 citation statements)

References 51 publications

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“…GRN mRNA was identified as one of the transcripts that were most strongly up-regulated by androgens in neonatal mouse hypothalami and in a series of elegant experiments by Suzuki et al (77) it was shown that depletion of PGRN blunts many of the normal masculine reproductive behaviors, particularly ejaculation. (78,79) Abrogation of the GRN gene in male mice showed unusual levels of anxiety, which were attributed at least in part to decreased expression of the serotonin receptor 5HT1A. (79) These findings coupled with the expression of PGRN in many regions of the embryonic mouse brain (51) hint at yet further roles for PGRN in brain development.…”

Section: Progranulin and Neurodegenerative Diseasesmentioning

confidence: 99%

“…(78,79) Abrogation of the GRN gene in male mice showed unusual levels of anxiety, which were attributed at least in part to decreased expression of the serotonin receptor 5HT1A. (79) These findings coupled with the expression of PGRN in many regions of the embryonic mouse brain (51) hint at yet further roles for PGRN in brain development. Intriguingly, comparative studies also support a key neuronal role for PGRN, since a PGRN-like protein is evident in the nerve cells of an annelid ragworm, whose last common ancestor with vertebrates presumably dates very early in animal evolution.…”

Section: Progranulin and Neurodegenerative Diseasesmentioning

confidence: 99%

“…(97) GRN knockout and transgenic models Grn knockout mice display behavioral abnormalities but few other recorded phenotypes. (79) Given the biological actions that have been attributed to PGRN, the mild knockout phenotype suggests that PGRN is a molecular generalist, contributing to many tasks but acutely essential for few. Dissecting the biological functions of PGRN is being revealed through conditional transgenic and knockout strategies.…”

Section: Progranulin Interaction With Other Proteinsmentioning

confidence: 99%

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The granulin gene family: from cancer to dementia

2009

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The growth factor progranulin (PGRN) regulates cell division, survival, and migration. PGRN is an extracellular glycoprotein bearing multiple copies of the cysteine-rich granulin motif. With PGRN family members in plants and slime mold, it represents one of the most ancient of the extracellular regulatory proteins still extant in modern animals. PRGN has multiple biological roles. It contributes to the regulation of early embryogenesis, to adult tissue repair and inflammation. Elevated PGRN levels often occur in cancers, and PGRN immunotherapy inhibits the growth of hepatic cancer xenografts in mice. Recent studies have demonstrated roles for PGRN in neurobiology. An autosomal dominant mutation in GRN, the gene for PGRN, leads to neuronal atrophy in the frontal and temporal lobes, resulting in the disease frontotemporal lobar dementia. In this review we will discuss current knowledge of the multifaceted biology of PGRN.

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Section: Progranulin and Neurodegenerative Diseasesmentioning

confidence: 99%

Section: Progranulin and Neurodegenerative Diseasesmentioning

confidence: 99%

Section: Progranulin Interaction With Other Proteinsmentioning

confidence: 99%

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The granulin gene family: from cancer to dementia

2009

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“…Therefore, functional in vivo and in vitro studies are needed. A GRN knockout (KO) mouse was generated to investigate its possible role in sexual differentiation [Kayasuga et al, 2007]. Increased aggressive behavior, elevated anxiety, and reduced mRNA expression of the serotonergic receptor 5-HT1A were observed in these mice [Kayasuga et al, 2007].…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

“…A GRN knockout (KO) mouse was generated to investigate its possible role in sexual differentiation [Kayasuga et al, 2007]. Increased aggressive behavior, elevated anxiety, and reduced mRNA expression of the serotonergic receptor 5-HT1A were observed in these mice [Kayasuga et al, 2007]. In relation to the FTLD phenotype, Kayasuga et al [2007] considered that behavioral disturbances in FTLD patients might be the result of a decreased serotonin level, indicating the potential involvement of GRN in the serotonergic system.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Granulin mutations associated with frontotemporal lobar degeneration and related disorders: An update

2008

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Communicated by Mark H. PaalmanMutations in the gene encoding granulin (HUGO gene symbol GRN, also referred to as progranulin, PGRN), located at chromosome 17q21, were recently linked to tau-negative ubiquitin-positive frontotemporal lobar degeneration (FTLDU). Since then, 63 heterozygous mutations were identified in 163 families worldwide, all leading to loss of functional GRN, implicating a haploinsufficiency mechanism. Together, these mutations explained 5 to 10% of FTLD. The high mutation frequency, however, might still be an underestimation because not all patient samples were examined for all types of loss-of-function mutations and because several variants, including missense mutations, have a yet uncertain pathogenic significance. Although the complete phenotypic spectrum associated with GRN mutations is not yet fully characterized, it was shown that it is highly heterogeneous, suggesting the influence of modifying factors. A role of GRN in neuronal survival was suggested but the exact mechanism by which neurodegeneration and deposition of pathologic brain inclusions occur still has to be clarified. Hum Mutat 29(12), [1373][1374][1375][1376][1377][1378][1379][1380][1381][1382][1383][1384][1385][1386] 2008.

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Aggression in non‐human vertebrates: Genetic mechanisms and molecular pathways

Freudenberg

Gutiérrez

Post

et al. 2015

American J of Med Genetics Pt B

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Aggression is an adaptive behavioral trait that is important for the establishment of social hierarchies and competition for mating partners, food, and territories. While a certain level of aggression can be beneficial for the survival of an individual or species, abnormal aggression levels can be detrimental. Abnormal aggression is commonly found in human patients with psychiatric disorders. The predisposition to aggression is influenced by a combination of environmental and genetic factors and a large number of genes have been associated with aggression in both human and animal studies. In this review, we compare and contrast aggression studies in zebrafish and mouse. We present gene ontology and pathway analyses of genes linked to aggression and discuss the molecular pathways that underpin agonistic behavior in these species.

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Alteration of behavioural phenotype in mice by targeted disruption of the progranulin gene

Cited by 176 publications

References 51 publications

The granulin gene family: from cancer to dementia

The granulin gene family: from cancer to dementia

Granulin mutations associated with frontotemporal lobar degeneration and related disorders: An update

Aggression in non‐human vertebrates: Genetic mechanisms and molecular pathways

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