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Robust axonal regeneration occurs in the injured CAST/Ei mouse central nervous system

ABSTRACT: Axon regeneration in the central nervous system (CNS) requires reactivating injured neurons’ intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice and show greater spouting following ischemic stroke. Heritability estimates indicate that extended growth in CAST/Ei neurons on myelin is genetically determined, and two whole-genome expression screens yield the Activin transcript Inhba as most correlated with this ability. These screens are presented here.

ORGANISM(S): Mus musculus

PROVIDER: GSE67130 | GEO | 2015/07/22

SECONDARY ACCESSION(S): PRJNA279017

REPOSITORIES: GEO

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Robust axonal regeneration occurs in the injured CAST/Ei mouse central nervous system

Project description:Axon regeneration in the central nervous system (CNS) requires reactivating injured neurons’ intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice and show greater spouting following ischemic stroke. Heritability estimates indicate that extended growth in CAST/Ei neurons on myelin is genetically determined, and two whole-genome expression screens yield the Activin transcript Inhba as most correlated with this ability. These screens are presented here. Biological quadruplicate - Mouse tissue - Naïve Dorsal Root Ganglia (DRG) and 5 day post sciatic nerve crush DRG - x9 strains.

2015-07-22 | E-GEOD-67130 | biostudies-arrayexpress

Regeneration occurs in the CNS of CAST/Ei mice as a consequence of enhanced Activin signaling

Project description:We screened nine genetically diverse inbred mouse strains for differences in axonal growth of adult dorsal root ganglion (DRG) neurons on CNS myelin. Naïve DRG neurite outgrowth on myelin was very limited, but preconditioning the neurons by a prior sciatic nerve crush increased axonal growth substantially across all strains, with by far the greatest change in neurons from CAST/Ei mice. Three independent in vivo CNS injury models revealed greater capacity for CNS axonal regeneration in CAST/Ei than C57BL/6 mice. Full-genome expression profiling of naïve and pre-conditioned DRGs across all strains revealed Activin-βA (Inhba) as the transcript whose expression most closely correlated with axonal growth on myelin. In vitro and in vivo gain- and loss-of-function experiments confirmed that Activin promotes axonal growth in the CNS. Substantial regeneration is possible, therefore, in the injured mammalian CNS when Activin signaling is intrinsically high, as in CAST/Ei or when extrinsically modulated in other strains.

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Regeneration occurs in the CNS of CAST/Ei mice as a consequence of enhanced Activin signaling

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Single cell sequencing of primary dorsal root ganglia from CAST/Ei or C57BL/6 mouse highlights strain differences in cellular populations.

Project description:Peripheral nerve regeneration after injury is a complex process involving a large number of transcriptional changes. How these changes impact the regenerative outcome is though, poorly understood. Here, we take advantage of the genetically based differences in the peripheral and central regenerative capacity of CAST/Ei and C57BL/6j inbred mice to better understand the molecular bases driving superior regeneration in the CAST/Ei mouse strain. Single cell RNA sequencing highlighted the existence of three populations of cells, one of which expressed genes enriched for mature neuronal function, another one had a gene expression profile enriched for an immature dedifferentiated state while the third one showed an intermediate profile between these two extremes. The immature expression state was observed after injury in both strains but a larger proportion of the CAST/Ei neurons retained an expression pattern consistent with neuronal identity whereas a larger proportion of C57BL/6 neurons acquired an immature gene expression state accompanied by expression of stress markers. This finding suggests that unexpectedly, maintenance of a mature differentiated state in injured neurons increased regenerative success.

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Increased physical activity accompanies carbohydrate preference in a B6.CAST-17 sub-congenic mouse strain

Project description:A C57BL6/J (B6) x CAST/Ei (CAST) strain intercross was used to identify the first mammalian QTL for macronutrient-specific intake (carbohydrate and fat) and for total energy intake. A region on proximal Chromosome 17 revealed two significant QTL that co-localized for increased macronutrient intake-carbohydrate (Mnic1) and total kilocalorie intake (Kcal2), adjusted for body weight. An interval-specific congenic strain, B6.CAST-17, was then developed which verified the QTL. A new sub-congenic strain was developed which retained the linked traits. Important new findings emerged shows that this congenic interval confers an activity phenotype, i.e., mice carrying the differential segment have 20% higher spontaneous physical activity levels compared with the host B6 strain. We hypothesize that this Chromosome 17 QTL is either encoded by a single gene locus that determines both food intake and physical activity, or by two or more genes, each determining a sub-phenotype of energy balance. Microarray analysis of skeletal muscle and hypothalamus in congenic and wild type B6 mice was carried out to identify potential candidate genes for the activity and food intake behavior. Keywords: macronutrient-specific intake, sub-congenic strain

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Mus musculus

Project description:Robust axonal regeneration occurs in the injured CAST/Ei mouse central nervous system

| PRJNA279017 | ENA