Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis

Bible, Ellen; Gupta, Praveena; Hofmann, Sandra L.; Cooper, Jonathan D.

doi:10.1016/j.nbd.2004.02.010

Cited by 166 publications

(280 citation statements)

References 43 publications

Supporting

Mentioning

263

Contrasting

Order By: Relevance

“…The expression of GFP and CD68 was measured by quantitative thresholding image analysis as previously described 13,48 with each antigen analysed blind to the type of vector injected. Briefly, 40 non-overlapping RGB images were captured across four consecutive sections through the CA1 subfield of the hippocampus, caudate putamen, motor and piriform cortex, medial septum, VPM/VPL region of the thalamus and the cerebellar nodule.…”

Section: Quantitative Analysis Of Immunohistochemical Stainingmentioning

confidence: 99%

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression

et al. 2011

View full text Add to dashboard Cite

The efficient delivery of genetic material to the developing fetal brain represents a powerful research tool and a means to supply therapy in a number of neonatal lethal neurological disorders. In this study, we have delivered vectors based upon adenovirus serotype 5 (Ad5) and adeno-associated virus (AAV) pseudotypes 2/5, 2/8 and 2/9 expressing green fluorescent protein to the E16 fetal mouse brain. One month post injection, widespread caudal to rostral transduction of neural cells was observed. In discrete areas of the brain these vectors produced differential transduction patterns. AAV2/8 and 2/9 produced the most extensive gene delivery and had similar transduction profiles. All AAV pseudotypes preferentially transduced neurons whereas Ad5 transduced both neurons and glial cells. None of the vectors elicited any significant microglia-mediated immune response when compared with control uninjected mice. Whole-body imaging and immunohistological evaluation of brains 9 months post injection revealed long-term expression using these non-integrating vectors. These data will be useful in targeting genetic material to discrete or widespread areas of the fetal brain with the purpose of devising therapies for early neonatal lethal neurodegenerative disease and for studying brain development.

show abstract

Section: Quantitative Analysis Of Immunohistochemical Stainingmentioning

confidence: 99%

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression

et al. 2011

View full text Add to dashboard Cite

show abstract

“…These estimates were performed as described previously. [26][27][28] In brief, a random starting section was chosen, followed by every sixth GFP-stained section thereafter. GFP-expressing cells were sampled using a series of counting frames distributed according to a grid superimposed onto the section.…”

Section: Stereological Quantification Of Egfp-positive Transduced Neumentioning

confidence: 99%

“…26,29 Briefly, 40 non-overlapping images were captured on 4 consecutive sections spanning the injection site of NILV/ ILV within the forebrain. Images were captured with a live video camera (JVC, 3CCD, KY-F55B), mounted onto a Zeiss Axioplan microscope using a Â 40 objective.…”

Section: Quantitative Analysis Of Lentiviral Expression In Adult Micementioning

confidence: 99%

Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors

et al. 2009

View full text Add to dashboard Cite

Non-integrating lentiviral vectors show considerable promise for gene therapy applications as they persist as long-term episomes in non-dividing cells and diminish risks of insertional mutagenesis. In this study, non-integrating lentiviral vectors were evaluated for their use in the adult and fetal central nervous system of rodents. Vectors differentially pseudotyped with vesicular stomatitis virus, rabies and baculoviral envelope proteins allowed targeting of varied cell populations. Efficient gene delivery to discrete areas of the brain and spinal cord was observed following stereotactic administration. Furthermore, after direct in utero administration (E14), sustained and strong expression was observed 4 months into adulthood. Quantification of transduction and viral copy number was comparable when using nonintegrating lentivirus and conventional integrating vector. These data support the use of non-integrating lentiviral vectors as an effective alternative to their integrating counterparts in gene therapy applications, and highlight their potential for treatment of inherited and acquired neurological disorders.

show abstract

“…Unbiased Cavalieri estimates of the volume of the substantia nigra pars compact and pars reticulata were made from six month male 129/SvJ and Cln3 -/-mice (n=4/test group) as described previously, with no prior knowledge of genotype (Bible et al, 2004;Pontikis et al, 2004). The boundaries of nuclei were defined by reference to landmarks in Paxinos and Franklin (Paxinos and Franklin, 2001).…”

Section: Measurements Of Substantia Nigra Volume and Cell Countsmentioning

confidence: 99%

“…For immunohistochemical analysis, brain samples were collected and sectioned as outlined above. Free floating sections were processed using standard immunohistochemical techniques as described previously (Bible et al, 2004). Antibodies used were tyrosine hydroxylase (Chemicon, Temecula, CA) and parvalbumin (Swant Inc, Bellinzona, Switzerland).…”

Section: Measurements Of Substantia Nigra Volume and Cell Countsmentioning

confidence: 99%

Alterations in striatal dopamine catabolism precede loss of substantia nigra neurons in a mouse model of juvenile neuronal ceroid lipofuscinosis

et al. 2007

View full text Add to dashboard Cite

Batten disease, or juvenile neuronal ceroid lipofuscinosis (JNCL), results from mutations in the CLN3 gene. This disorder presents clinically around the age of five years with visual deficits progressing to include seizures, cognitive impairment, motor deterioration, hallucinations, and premature death by the third to forth decade of life. The motor deficits include coordination and gait abnormalities, myoclonic jerks, inability to initiate movements, and spasticity. Previous work from our laboratory has identified an early reduction in catechol-O-methyltransferase (COMT), an enzyme responsible for the efficient degradation of dopamine. Alterations in the kinetics of dopamine metabolism could cause the accumulation of undegraded or unsequestered dopamine leading to the formation of toxic dopamine intermediates. We report an imbalance in the catabolism of dopamine in three month Cln3 -/-mice persisting through nine months of age that may be causal to oxidative damage within the striatum at nine months of age. Combined with the Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript previously reported inflammatory changes and loss of post-synaptic D1α receptors, this could facilitate cell loss in striatal projection regions and underlie a general locomotion deficit that becomes apparent at twelve months of age in Cln3 -/-mice. This study provides evidence for early changes in the kinetics of COMT in the Cln3 -/-mouse striatum, affecting the turnover of dopamine, likely leading to neuron loss and motor deficits. These data provide novel insights into the basis of motor deficits in JNCL and how alterations in dopamine catabolism may result in oxidative damage and localized neuronal loss in this disorder.

show abstract

Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis

Cited by 166 publications

References 43 publications

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression

Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors

Alterations in striatal dopamine catabolism precede loss of substantia nigra neurons in a mouse model of juvenile neuronal ceroid lipofuscinosis

Contact Info

Product

Resources

About