Phenotypes associated with this allele

• Allele Symbol: Tecr^tm1.1Migar
• Allele Name: targeted mutation 1.1, Michihiro Igarashi
• Allele ID: MGI:7868156
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tecr^tm1.1Migar/Tecr^tm1.1Migar	B6N.Cg-Tecr^tm1.1Migar	MGI:8204683
ht2	Tecr^tm1.1Migar/Tecr^+	B6N.Cg-Tecr^tm1.1Migar	MGI:8204688

Genotype
MGI:8204683

hm1

• Allelic Composition: Tecr^tm1.1Migar/Tecr^tm1.1Migar
• Genetic Background: B6N.Cg-Tecr^tm1.1Migar

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:342152 )

• no homozygotes are observed at E11.5-E13.5 or at P1; viable homozygotes are last recovered in Mendelian ratios at E9.5-E10.0

embryo

impaired somite development ( J:342152 )

• at E9.5, somite number is 24 versus 30 in wild-type embryos

abnormal amnion morphology ( J:342152 )

• homozygous embryos exhibit a substantially regressed amnion by E11.5

nervous system

abnormal nervous system development ( J:342152 )

• at E9.5, nervous system development is delayed with severe inhibition of axon and network formation

abnormal axon extension ( J:342152 )

• at E9.5, axonal projections of the petrosal ganglion and dorsal root ganglion (DRG) are significantly reduced

delayed axon extension ( J:342152 )

• axonal projections from the cranial nerve and dorsal root ganglia (DRG) ganglia are delayed

impaired neuron differentiation ( J:342152 )

• neuronal development is severely inhibited in both the CNS and PNS

abnormal midbrain development ( J:342152 )

• at E9.5, the midbrain remains immature and displays retarded extension

delayed brain development ( J:342152 )

abnormal neurite morphology ( J:342152 )

• at E9.5, neural projections from the ventral neurons located in the diencephalon and mesencephalon are significantly decreased in number

• trigeminal ganglia projections toward the cerebellar primordium and the ascending components of the trigeminal ganglia-derived fibers display impaired formation

abnormal cranial nerve morphology ( J:342152 )

• at E9.5, the cranial nerves remain immature and display retarded extension

absent hypoglossal nerve ( J:342152 )

• no hypoglossal nerve (XII cranial nerve) is found

homeostasis/metabolism

decreased fatty acids level ( J:342152 )

• both free and bound very-long-chain fatty acids (VLCFAs) are decreased

• free FAs involved in C24:1 and C24:2 synthesis are significantly decreased

decreased ceramide level ( J:342152 )

• VLCFA-containing ceramide is reduced; ceramide-C24 and ceramide with >C24 FAs are significantly decreased in a VLCFA-dependent manner

abnormal glycosphingolipid level ( J:342152 )

• hexosylceramide (a type of glycosphingolipid) with C26 or longer FA chains is reduced independent of VLCFAs

abnormal lipogenesis ( J:342152 )

• at E9.5, dihydroceramide synthesis is inhibited in a fatty acid (FA) chain length-dependent manner

• sphingolipids downstream of ceramide show a marked reduction in FAs with acyl chains of C20 or longer; the amount of C24 FAs is largely decreased

• amount of dihydrosphingosine, an upstream product of ceramide, is highly increased

• in contrast, changes in the amount of glycerophospholipids are not dependent upon FA chains

cellular

abnormal axon extension ( J:342152 )

• at E9.5, axonal projections of the petrosal ganglion and dorsal root ganglion (DRG) are significantly reduced

delayed axon extension ( J:342152 )

• axonal projections from the cranial nerve and dorsal root ganglia (DRG) ganglia are delayed

impaired neuron differentiation ( J:342152 )

• neuronal development is severely inhibited in both the CNS and PNS

Genotype
MGI:8204688

ht2

• Allelic Composition: Tecr^tm1.1Migar/Tecr⁺
• Genetic Background: B6N.Cg-Tecr^tm1.1Migar

nervous system

delayed axon extension ( J:342152 )

• axonal growth of dorsal root ganglia (DRG) is impeded

impaired neuron differentiation ( J:342152 )

• severe defects in neuronal development are due to impaired neuronal polarity determination

abnormal neuron polarity ( J:342152 )

• cultured E14.5 hippocampal neurons exhibit a multipolar form characterized by multiple, shorter axons and absence of Pard3 (par-3 family cell polarity regulator, aka Par3) accumulation in the axon growth cone, indicating impaired neuronal polarity

• neurons show a lack of lipid rafts in the growth cone, as indicated by a significant decrease in the lipid-ordered (Lo)-phase area (marking lipid-raft domains) and reduced expression of neuronal lipid raft markers (e.g. GPM6a and GM1 ganglioside)

• GPSN2 overexpression in the growth cone rescues the % of polarized hippocampal neurons with a single axon and restores axon length to wild-type values

• application of VLCFA-ceramide (C24:0 ceramide), but not C16:0 ceramide or C24:0 phosphatidylcholine, to heterozygous neurons rescues both neuronal polarity determination and lipid-raft density in the growth cone

abnormal hypoglossal nerve morphology ( J:342152 )

• hypoglossal nerve (XII cranial nerve) is shorter than in wild-type embryos

homeostasis/metabolism

decreased fatty acids level ( J:342152 )

• free FAs involved in C24:1 and C24:2 synthesis are significantly decreased

decreased ceramide level ( J:342152 )

• ceramide-C24 and ceramide with >C24 FAs are significantly decreased in a VLCFA-dependent manner

abnormal glycosphingolipid level ( J:342152 )

• hexosylceramide (a type of glycosphingolipid) with C26 or longer FA chains is reduced independent of VLCFAs

decreased ganglioside level ( J:342152 )

• major ganglioside species (GD3, GM1, and GM3) are significantly decreased in the growth cone membrane (GCM) of neurons from E16 brains but not in the whole-cell membrane (WCM, i.e. entire neuronal membrane)

• various GCM gangliosides are decreased, and this change is mirrored by relative increases in WCM for many ganglioside species

abnormal lipogenesis ( J:342152 )

• at E9.5, sphingolipids downstream of ceramide show a marked reduction in fatty acids (FAs) with acyl chains of C20 or longer; the amount of C24 FAs is largely decreased

cellular

delayed axon extension ( J:342152 )

• axonal growth of dorsal root ganglia (DRG) is impeded

impaired neuron differentiation ( J:342152 )

• severe defects in neuronal development are due to impaired neuronal polarity determination