Table 2 RASopathy mouse models and their phenotypes

Nf1

Nf1 homozygous knockout

Defects in the neural tube, hyperplasia of neural crest-derived ganglia [75]

Embryonic lethality, heart defects, delay in organ development [76, 77]

Nf1 heterozygous knockout

Increased number of astrocytes [78, 79]

Impaired synaptic plasticity, impaired spatial learning, heart defects [80,81,82]

Synapsin 1-dependent Nf1 ablation

Reduced size and weight of the forebrain, reduced cortical thickness, increased astrogliogenesis [83]

Learning deficits, growth retardation [83, 84]

hGFAP-dependent Nf1 ablation

Increased gliogenesis, enlarged cerebral cortex, defective GNP migration and proliferation

[85,86,87,88]

Postnatal lethality, growth retardation [86, 87]

BLBP-dependent Nf1 ablation

Increased 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]

Ptpn11

Nestin-dependent Ptpn11 ablation

Decreased neural stem cell proliferation, lamination defects, reduced number of neurons, increased number of astrocytes [92]

Postnatal lethality, growth retardation [92]

Olig1-dependent Ptpn11 ablation

Decreased number of oligodendrocyte precursors and mature oligodendrocytes, reduced axonal myelination [93]

Developmental abnormalities [93]

Olig2-dependent Ptpn11 ablation

Decreased number of oligodendrocyte precursors, hypomyelination [94]

Postnatal lethality, severe shivering [94]

Olig2-dependent Ptpn11^Q79R knock-in

Increased number of oligodendrocyte precursors, abnormal myelination [94]

Not described

Nestin-dependent Ptpn11^E76K knock-in

Hydrocephalus, aberrant development of ependymal cells, reduced proliferation, enhanced glial differentiation [95]

Postnatal lethality, dome-shaped head, reduced anxiety behavior, hyperactivity, impaired motor function [95]

Ptpn11^D61G herozygous knock-in

Increased neurogenesis, decreased gliogenesis [96]

Impaired synaptic plasticity, impaired spatial learning, short stature, craniofacial dysmorphia [97, 98]

Kras

Synapsin1-dependent Kras^G12V knock-in

Enhanced GABAergic synaptogenesis [99]

Increased inhibitory tone, impaired spatial learning [99]

Hras

Hras^G12V homozygous knock-in

Hypertrophy of the brain and pyramidal neurons [100]

Impaired spatial learning, facial dysmorphia, cardiac defects [100]

aCaMKII-dependent Hras^G12V knock-in

Increase in docked vesicles [101]

Increased synaptic plasticity, enhanced spatial learning [101]

Braf

Nestin-dependent Braf ablation

Impaired neuronal differentiation, dysmyelination, defective oligodendrocyte differentiation [102, 103]

Postnatal lethality, growth retardation, defective motor coordination, neuromuscular defects [102, 103]

Braf^V600E heterozygous knock-in

Increased number of GFAP positive cells in the DG [104]

Reduced life span, growth retardation, facial dysmorphia, cardiomegaly, epileptic seizures [104]

Raf1

Raf1 heterozygous knockout

Small granule cell volume, increased cell death, reduced neuronal maturation [105]

Postnatal lethality, growth retardation, apoptosis in the lung and liver, limbs coordination problems [106]

Raf1^L613V heterozygous knock-in

Increased density of astrocytes, enhanced OPCs density [107]

Enhanced learning and memory [107]

Mek1/2

Mek1^Y130C homozygous knock-in

Increased astrocyte density, increased number of cortical oligodendrocytes [108]

Pulmonary artery stenosis, cranial dysmorphia [108]

Nestin-dependent Mek1/2 ablation

Decrease of astrocyte precursors and OPCs, failure of gliogenesis [109]

Early postnatal lethality [109]

hGFAP-dependent Mek1/2 ablation

Suppressed generation of astrocyte precursors and OPCs, failure of gliogenesis [109]

Postnatal lethality [109]

hGFAP-dependent Mek1^S218E,S222E

Increase in astrocyte precursors and mature astrocytes, reduction of neuron number [109]

Not described