TY  - JOUR
AB  - The ability to exert complex locomotor behaviors requires precise guidance of sensory and motor fibers to the extremities, resulting in the formation of precise peripheral networks. Interactions of growing axons with their environment and co-extending nerve fibers have been shown to critically contribute to the establishment of neuronal projections to the limb, governing accurate fasciculation of heterotypic fiber systems and mediating the stereotypic dorsal-ventral guidance decisions of growing motor axons at the base of the limb. Here we provide a detailed methodology to quantitate selective fasciculation of axon tracts at specific choice points as well as guidance fidelity of motor neurons projecting to the dorsal or ventral limb during embryonal development. Immunohistochemical staining of whole-mount embryo preparations was employed to analyze patterned growth of axons towards the plexus region, and selective branching beyond this choice point. Retrograde tracing of motor neurons from the dorsal or ventral limb mesenchyme served to analyze stereotypical dorsal-ventral guidance decisions of motor neurons localized in the medial and lateral aspects of the lateral motor column (LMC). These methods therefore provide a valuable tool to reliably quantify sensory-motor fasciculation and stereotypic guidance events during early embryonal development.
AU  - Hüttl, R.E.
AU  - Huber, A.B.
C1  - 31223
C2  - 34213
SP  - 145-162
TI  - Quantitative analysis of axonal outgrowth in mice.
JO  - Neuromethods
VL  - 87
PY  - 2014
SN  - 1940-6045
ER  - 

TY  - BOOK
AB  - Here, we describe the systematic mouse phenotyping approach of the German Mouse Clinic (GMC), that works as an open-access phenotyping platform, and of the European Mouse Disease Clinic, which is an EU-funded multi-centre project characterising mutants generated by the large-scale mouse mutagenesis project European Conditional Mouse Mutagenesis Program. We explain the aims and the general framework of these large-scale projects and the resulting consequences for the phenotyping strategies. Then, we focus on the description of the behavioural tests used in the GMC to detect motor and nonmotor symptoms in mouse mutants that are genetic models of human movement disorders or neurodegenerative diseases.
AU  - Hölter, S.M.
AU  - Glasl, L.
A2  - Lane, E.L.* ; Dunnett, S.B.*
C1  - 6820
C2  - 29314
CY  - New York, NY
SP  - 109-133
TI  - High-troughput mouse phenotyping.
JO  - Neuromethods
VL  - 61
PB  - Human Press
PY  - 2011
SN  - 1940-6045
ER  - 

TY  - BOOK
AB  - Parkinson’s disease (PD) is a chronic, progressive neurodegenerative movement disorder. To understand the pathomechanisms and to develop new drugs and therapies for PD, it is important to have animal models that recapitulate the slow progression and symptoms of the disease. The generation of genetic animal models of genes responsible for autosomal dominant but also autosomal recessive forms of PD has indeed accelerated our understanding of these pathomechanisms. To model the effect of dominant mutant alleles, transgenic mice were produced that express mutation-bearing proteins in neurons. To model lossof- function alleles, knockout mice were generated and studied. However, none of these models recapitulate PD disease as it occurs in PD patients. The latest mouse genetic technology may offer, at least in part, a relief for these challenges through the timed control of protein expression or gene knockout. Both can be achieved by the use of the Tamoxifen inducible CreERT2 gene switch that enables the inducible activation of transgene expression or inducible gene knockout. Thereby the CreERT2 system can be used to generate genetic models of gain-of-function (dominant) disease-associated alleles by the regulated expression of mutant coding regions as well as to model loss-of-function (recessive) disease-associated alleles by inducible gene knockout. In this chapter, we cover the design of such Tamoxifen inducible transgene constructs and the use of premade conditional knockout alleles generated by large-scale mutagenesis projects. Furthermore, we provide an overview of the available brain-specific CreERT2 mouse lines, notes on the control groups for inducible knockout experiments and a protocol for Tamoxifen administration.
AU  - Kühn, R.
AU  - Vogt Weisenhorn, D.M.
AU  - Wurst, W.
C1  - 6819
C2  - 29313
CY  - New York, NY
SP  - 243-265
TI  - Genetic models of Parkinson's disease.
JO  - Neuromethods
VL  - 61
PB  - Humana Press
PY  - 2011
SN  - 1940-6045
ER  -