Heterozygous L1-deficient mice express an autism-like phenotype

Sauce, Bruno; Wass, Christopher; Netrakanti, Meera; Saylor, Joshua; Schachner, Melitta; Matzel, Louis D.

doi:10.1016/j.bbr.2015.05.040

Cited by 17 publications

(27 citation statements)

References 45 publications

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“…Immunohistology was performed as described (McDonough et al, 2015 ; Sauce et al, 2015 ). At different time points (3, 7, 14 and 28 days) after SCI, mice were anesthetized with isopentane (Baxter Healthcare Puerto Rico, Guayama, Puerto Rico) by inhalation and perfused via cardiac puncture first with PBS and then with 4% formaldehyde in PBS (Tang et al, 2015 ; Wang et al, 2015 ).…”

Section: Methodsmentioning

confidence: 99%

Electroacupuncture Restores Locomotor Functions After Mouse Spinal Cord Injury in Correlation With Reduction of PTEN and p53 Expression

Wei

Zhao

Schachner

2018

Front. Mol. Neurosci.

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Background: We previously showed that electroacupuncture (EA) at Jiaji points promotes expression of adhesion molecule L1 in spinal cord tissue after mouse spinal cord injury (SCI) and contributes to recovery of neural functions.Objective: We investigated the effects of EA on downstream signaling molecules of L1 and molecules relevant to apoptosis with the aim to understand the underlying molecular mechanisms.Methods: Female C57BL/6 mice were divided into a sham group, injury group, injury+acupuncture (AP) group and injury+EA group. We investigated the changes in cognate L1-triggered signaling molecules after SCI by immunofluorescence staining and immunoblot analysis.Results: Protein levels of phosphatase and tensin homolog (PTEN) and p53 were decreased by EA at different time points after injury, whereas the levels of phosphorylated mammalian target of rapamycin (pmTOR), p-Akt and phosphorylated extracellular signal-regulatedkinase (p-Erk) were increased. Also, levels of myelin basic protein (MBP) were increased by EA. AP alone showed less pronounced changes in expression of the investigated molecules, when compared to EA.Conclusion: We propose that EA contributes to neuroprotection by inhibiting PTEN and p53 expression and by increasing the levels of pmTOR/Akt/Erk and of MBP after SCI. These observations allow novel insights into the beneficial effects of EA via L1-triggered signaling molecules after injury.

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Section: Methodsmentioning

confidence: 99%

Electroacupuncture Restores Locomotor Functions After Mouse Spinal Cord Injury in Correlation With Reduction of PTEN and p53 Expression

Wei

Zhao

Schachner

2018

Front. Mol. Neurosci.

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“…We used the mean distance traveled (path length) by each mouse from Trials 2 to 6 as a measure of the rate of spatial learning. These trials seem to be a good indicator of differences in rate of acquisition, and we have used them elsewhere for this purpose (Kolata, Wu, Light, Schachner, & Matzel, 2008; Sauce et al, 2015). As expected, we found that, across all mice, the rate of learning was not significantly predicted by persistence in the Long Alley, β=0.29, t(22)=1.421, p>0.250, R 2 =0.08.…”

Section: Resultsmentioning

confidence: 99%

A broader phenotype of persistence emerges from individual differences in response to extinction

et al. 2017

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The typical practice of averaging group performance during extinction gives the impression that responding declines gradually and homogeneously. However, previous studies of extinction in human infants have shown that some individuals persist in responding, whereas others abruptly cease responding. As predicted by theories of control, the infants who quickly resign typically display signs of sadness and despair when the expected reward is omitted. Using genetically diverse mice, here we observed a similar pattern of individual differences and the associated phenotypes. After learning to approach a food reward, upon extinction, some animals rapidly abandoned approach to the goal box, whereas other animals persisted in entering and searching the goal box. Interestingly, the persistent mice were slower to "give up" when confined to an inescapable pool of water (a test asserted to be indicative of susceptibility to depression) and exhibited a more extensive pattern of search for omitted rewards. Thus, extinction reveals a continuum in persistence, in which low values might reflect a susceptibility to the negative effects of stress and might predispose individuals to depression.

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“…The C.elegans protein, SAX-7, interacts with menorin to control the dendritic branching of sensory neurons 5 . Mutants of the mammalian homologue of Sax-7, L1CAM, have been described as having abnormal axon guidance and retinal ganglion cells, as well as other neuronal problems [18][19][20][21] . This phenotype has similarities to that seen in C. elegans mutants, and has implicated L1CAM in the precise guidance of axons.…”

Section: Discussionmentioning

confidence: 99%

Fam151b, the mouse homologue of C.elegans menorin gene, is essential for retinal function

Findlay

McKie

Keighren

et al. 2020

Sci Rep

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Fam151b is a mammalian homologue of the C. elegans menorin gene, which is involved in neuronal branching. the international Mouse phenotyping consortium (iMpc) aims to knock out every gene in the mouse and comprehensively phenotype the mutant animals. This project identified Fam151b homozygous knock-out mice as having retinal degeneration. We show they have no photoreceptor function from eye opening, as demonstrated by a lack of electroretinograph (eRG) response. Histological analysis shows that during development of the eye the correct number of cells are produced and that the layers of the retina differentiate normally. However, after eye opening at P14, Fam151b mutant eyes exhibit signs of retinal stress and rapidly lose photoreceptor cells. We have mutated the second mammalian menorin homologue, Fam151a, and homozygous mutant mice have no discernible phenotype. Sequence analysis indicates that the FAM151 proteins are members of the pLc-like phosphodiesterase superfamily. However, the substrates and function of the proteins remains unknown.The retina is the light sensitive tissue located in the posterior eye. Photoreceptor cells within the retina are responsible for converting light signals into electrical signals, and loss of these cells is a leading cause of blindness in humans. In the course of diseases such as retinitis pigmentosa (RP), rod and cone photoreceptor cells are slowly lost, beginning at the peripheral retina and moving centrally 1 . Multiple mutant genes in humans can cause RP, and many of these have counterpart mouse models 2 . In this paper we describe a novel mouse model of retinal degeneration which has early and rapid loss of photoreceptor cells due to loss of function of a largely uncharacterised gene. The International Mouse Phenotyping Consortium (IMPC) is a worldwide collaborative effort to generate lines of mice, each with a loss of function mutation in a single gene, and to comprehensively phenotype the lines 3,4 . The ultimate aim is to catalogue the function of every gene in the mouse genome in order to contribute to the understanding of fundamental mammalian biology and to generate models for human disease. Many institutions participate and follow an agreed pipeline for the phenotypic analysis of the mice, known as IMPReSS (International Mouse Phenotyping Resource of Standardised Screen). The analyses include growth, morphological, behavioural, metabolic and sensory phenotypes over a 15 week period, and followed post-mortem by examination of haematology, immunology, clinical chemistry and gross pathology. At 15 weeks of age mutant mice undergo slit lamp examination and ophthalmoscopy to investigate the gross morphology of the eye.As part of this study a novel gene, Fam151b, was mutated and the mice analysed through the IMPC pipeline. Fam151b knockout mice were found to have abnormal retina morphology and no other observed phenotype.Here we follow up these findings with a detailed histological and functional analysis of this disease model. In addition we have mutated the paralogous...

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Heterozygous L1-deficient mice express an autism-like phenotype

Cited by 17 publications

References 45 publications

Electroacupuncture Restores Locomotor Functions After Mouse Spinal Cord Injury in Correlation With Reduction of PTEN and p53 Expression

Electroacupuncture Restores Locomotor Functions After Mouse Spinal Cord Injury in Correlation With Reduction of PTEN and p53 Expression

A broader phenotype of persistence emerges from individual differences in response to extinction

Fam151b, the mouse homologue of C.elegans menorin gene, is essential for retinal function

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