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Table 2 RASopathy mouse models and their phenotypes

From: The impact of RASopathy-associated mutations on CNS development in mice and humans

GeneMouse modelCNS structural phenotypesOther phenotypes
Nf1Nf1 homozygous knockoutDefects in the neural tube, hyperplasia of neural crest-derived ganglia [75]Embryonic lethality, heart defects, delay in organ development [76, 77]
Nf1 heterozygous knockoutIncreased number of astrocytes [78, 79]Impaired synaptic plasticity, impaired spatial learning, heart defects [80,81,82]
Synapsin 1-dependent Nf1 ablationReduced size and weight of the forebrain, reduced cortical thickness, increased astrogliogenesis [83]Learning deficits, growth retardation [83, 84]
hGFAP-dependent Nf1 ablationIncreased gliogenesis, enlarged cerebral cortex, defective GNP migration and proliferation
[85,86,87,88]
Postnatal lethality, growth retardation [86, 87]
BLBP-dependent Nf1 ablationIncreased glial lineage proliferation, abnormal neuronal differentiation [89]Postnatal lethality [89]
Nestin-dependent Nf1 ablation (induction in adulthood)Unlocked latent oligodendrocyte lineage, defective GNP proliferation and migration, increased adult hippocampal neurogenesis [88, 90, 91]Spontaneous antidepressive-like behavior [91]
Ptpn11Nestin-dependent Ptpn11 ablationDecreased neural stem cell proliferation, lamination defects, reduced number of neurons, increased number of astrocytes [92]Postnatal lethality, growth retardation [92]
Olig1-dependent Ptpn11 ablationDecreased number of oligodendrocyte precursors and mature oligodendrocytes, reduced axonal myelination [93]Developmental abnormalities [93]
Olig2-dependent Ptpn11 ablationDecreased number of oligodendrocyte precursors, hypomyelination [94]Postnatal lethality, severe shivering [94]
Olig2-dependent Ptpn11Q79R knock-inIncreased number of oligodendrocyte precursors, abnormal myelination [94]Not described
Nestin-dependent Ptpn11E76K knock-inHydrocephalus, aberrant development of ependymal cells, reduced proliferation, enhanced glial differentiation [95]Postnatal lethality, dome-shaped head, reduced anxiety behavior, hyperactivity, impaired motor function [95]
Ptpn11D61G herozygous knock-inIncreased neurogenesis, decreased gliogenesis [96]Impaired synaptic plasticity, impaired spatial learning, short stature, craniofacial dysmorphia [97, 98]
KrasSynapsin1-dependent KrasG12V knock-inEnhanced GABAergic synaptogenesis [99]Increased inhibitory tone, impaired spatial learning [99]
HrasHrasG12V homozygous knock-inHypertrophy of the brain and pyramidal neurons [100]Impaired spatial learning, facial dysmorphia, cardiac defects [100]
aCaMKII-dependent HrasG12V knock-inIncrease in docked vesicles [101]Increased synaptic plasticity, enhanced spatial learning [101]
BrafNestin-dependent Braf ablationImpaired neuronal differentiation, dysmyelination, defective oligodendrocyte differentiation [102, 103]Postnatal lethality, growth retardation, defective motor coordination, neuromuscular defects [102, 103]
BrafV600E heterozygous knock-inIncreased number of GFAP positive cells in the DG [104]Reduced life span, growth retardation, facial dysmorphia, cardiomegaly, epileptic seizures [104]
Raf1Raf1 heterozygous knockoutSmall granule cell volume, increased cell death, reduced neuronal maturation [105]Postnatal lethality, growth retardation, apoptosis in the lung and liver, limbs coordination problems [106]
Raf1L613V heterozygous knock-inIncreased density of astrocytes, enhanced OPCs density [107]Enhanced learning and memory [107]
Mek1/2Mek1Y130C homozygous knock-inIncreased astrocyte density, increased number of cortical oligodendrocytes [108]Pulmonary artery stenosis, cranial dysmorphia [108]
Nestin-dependent Mek1/2 ablationDecrease of astrocyte precursors and OPCs, failure of gliogenesis [109]Early postnatal lethality [109]
hGFAP-dependent Mek1/2 ablationSuppressed generation of astrocyte precursors and OPCs, failure of gliogenesis [109]Postnatal lethality [109]
hGFAP-dependent Mek1S218E,S222EIncrease in astrocyte precursors and mature astrocytes, reduction of neuron number [109]Not described
  1. hGFAP Human glial fibrillary acidic protein, BLBP Brain lipid binding protein, GNP Granule neuron progenitor, DG Dentate gyrus, OPCs Oligodendrocyte progenitor cells