Increased Anxiety and Impaired Pain Response in Puromycin-Sensitive Aminopeptidase Gene-Deficient Mice Obtained by a Mouse Gene-Trap Method

Osada, Tomoharu; Ikegami, Shiro; Takiguchi-Hayashi, Keiko; Yamazaki, Yukiko; Katoh‐Fukui, Yuko; Higashinakagawa, Toru; Sakaki, Yoshiyuki; Takeuchi, Takashi

doi:10.1523/jneurosci.19-14-06068.1999

Cited by 73 publications

(49 citation statements)

References 29 publications

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“…DISCUSSION The present study describes the role of the puromycin-sensitive aminopeptidase, PAM-1, in the biology of the free-living nematode C. elegans. The expression pattern analysis shows that PAM-1 is expressed throughout development, and the neuronal component is consistent with PSA localization reported for other organisms (4,31). This may reflect an evolutionary conserved role for PSA in the processing of neuropeptides.…”

Section: Resultssupporting

confidence: 86%

“…The puromycin-sensitive aminopeptidase (PSA 1 ; EC 3.4.11.14) is a member of the M1 family of metallopeptidases, and, as such, it possesses the archetypal HEXXH(X) 18 E metal ion coordination site and the GAMEN motif characteristic of this family (2). A membrane-associated PSA is found in rat brain tissue (3), and studies using mouse mutants have shown that this isoform is involved in growth and behaviors associated with anxiety and pain (4). Further characterization has shown that this membrane PSA is essential for fertility in male and female mice (5,6).…”

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confidence: 99%

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The Caenorhabditis elegans Orthologue of Mammalian Puromycin-sensitive Aminopeptidase Has Roles in Embryogenesis and Reproduction

Brooks

Hooper

Isaac

2003

Journal of Biological Chemistry

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Peptide hydrolysis was inhibited by the metal-chelating agent 1,10-phenanthroline and by the aminopeptidase inhibitors actinonin, amastatin, and leuhistin. However, the enzyme was ϳ100-fold less sensitive toward puromycin (IC 50 , 135 M) than other PSA homologues. Following inactivation of the enzyme, aminopeptidase activity was recovered with Zn 2؉ , Co 2؉ , and Ni 2؉ . Silencing expression of pam-1 by RNA interference resulted in 30% embryonic lethality. Surviving adult hermaphrodites deposited large numbers of oocytes throughout the selffertile period. The overall brood size was, however, unaffected. We conclude that pam-1 encodes an aminopeptidase that clusters phylogenetically with the PSAs, despite attenuated sensitivity toward puromycin, and that it functions in embryo development and reproduction of the nematode.

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Section: Resultssupporting

confidence: 86%

mentioning

confidence: 99%

The Caenorhabditis elegans Orthologue of Mammalian Puromycin-sensitive Aminopeptidase Has Roles in Embryogenesis and Reproduction

Brooks

Hooper

Isaac

2003

Journal of Biological Chemistry

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“…The rod working test was performed using an iron rod 70 cm long and 90 mm in diameter wrapped with a masking tape. The experiment was performed as described elsewhere (13).…”

Section: Methodsmentioning

confidence: 99%

Neurochondrin Negatively Regulates CaMKII Phosphorylation, and Nervous System-specific Gene Disruption Results in Epileptic Seizure

Dateki

Horii

Kasuya

et al. 2005

Journal of Biological Chemistry

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Neurochondrin is a novel cytoplasmic protein and possibly involved in neurite outgrowth, chondrocyte differentiation, and bone metabolism. Our previous trial in disclosing its role by the loss of function in mice failed because of the lethality in utero. In this study, we eliminated the neurochondrin gene expression preferentially in the nervous system by the conditional knockout strategy. Our results showed that neurochondrin is a negative regulator of Ca 2؉ /calmodulin-dependent protein kinase II phosphorylation and essential for the spatial learning process but not for the differentiation or neurite outgrowth of the neuron. In addition, the nervous system-specific homozygous gene disruption resulted in epileptic seizure.

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“…Histological examination was performed as described previously (Osada et al, 1999). Under anesthesia with avertin, mice were perfused transcardially with ice-cold 4% paraformaldehyde in PBS.…”

Section: Methodsmentioning

confidence: 99%

Developmental Pluripotency of the Nuclei of Neurons in the Cerebral Cortex of Juvenile Mice

Osada¹,

Tamamaki²,

Song³

et al. 2005

J. Neurosci.

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Nuclei isolated from green fluorescent protein-marked neurons in the cerebral cortex of juvenile mice (14 -21 d after birth) were injected into enucleated oocytes that were allowed to develop into blastocysts. Embryonic stem (ES) cell lines were established from the inner cell mass of 76 cloned blastocysts after injecting 2026 neuronal nuclei. Some ES cells were injected individually into enucleated oocytes (nuclear transfer). Other ES cells were transferred into the blastocoeles of tetraploid blastocysts (tetraploid complementation). Two-cell embryos after nuclear transfer were transferred to the oviducts of surrogate mothers. Four (1.5%) of 272 nuclear-transferred two-cell embryos developed to term, and two (0.7%) developed into fertile adults. Nineteen (1.9%) of 992 tetraploid blastocysts receiving ES cells reached term, and 10 (1.0%) developed into adults. These findings demonstrate that some of the nuclei of differentiated neurons in the cerebral cortex of juvenile mice maintain developmental pluripotency.

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Increased Anxiety and Impaired Pain Response in Puromycin-Sensitive Aminopeptidase Gene-Deficient Mice Obtained by a Mouse Gene-Trap Method

Cited by 73 publications

References 29 publications

The Caenorhabditis elegans Orthologue of Mammalian Puromycin-sensitive Aminopeptidase Has Roles in Embryogenesis and Reproduction

The Caenorhabditis elegans Orthologue of Mammalian Puromycin-sensitive Aminopeptidase Has Roles in Embryogenesis and Reproduction

Neurochondrin Negatively Regulates CaMKII Phosphorylation, and Nervous System-specific Gene Disruption Results in Epileptic Seizure

Developmental Pluripotency of the Nuclei of Neurons in the Cerebral Cortex of Juvenile Mice

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