Phenotypes associated with this allele

• Allele Symbol: Ttll7^tm1Seto
• Allele Name: targeted mutation 1, Mitsutoshi Setou
• Allele ID: MGI:6476783
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ttll7^tm1Seto/Ttll7^tm1Seto	B6;129-Ttll7^tm1Seto/SetoRbrc	MGI:7783461
cx2	Ttll1^tm1Seto/Ttll1^tm1Seto Ttll7^tm1Seto/Ttll7^tm1Seto	involves: 129 * 129S/SvEv * C57BL/6J	MGI:7783462
cx3	Ttll1^tm1Seto/Ttll1^+ Ttll7^tm1Seto/Ttll7^tm1Seto	involves: 129 * 129S/SvEv * C57BL/6J	MGI:7783467

Genotype
MGI:7783461

hm1

• Allelic Composition: Ttll7^tm1Seto/Ttll7^tm1Seto
• Genetic Background: B6;129-Ttll7^tm1Seto/SetoRbrc

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

growth/size/body

increased body weight ( J:345300 )

• mice are significantly heavier than wild-type controls

behavior/neurological

behavioral despair ( J:345300 )

• in the Porsolt forced swim test, mice show a significantly increased immobility posture, and a significantly shorter distance traveled in the first 5 min block of day 1, indicating increased depression-like behavior during the initial period

impaired coordination ( J:345300 )

• in the wire hang test, the latency to fall off the wire mesh is significantly shorter than in wild-type controls

• however, forelimb grip strength is normal

increased locomotor activity ( J:345300 )

• in the social interaction test in the home cage, mice exhibit a significantly increased mean of particles during the dark period, suggesting increased locomotor activity during the night

• in the elevated plus maze test, the distance traveled during the first 5 min block of the test is significantly greater than in wild-type controls; however, the total distance traveled over the 10 min test period is normal

nervous system

nervous system phenotype ( J:345300 )

N • mice exhibit normal brain weight relative to wild-type controls; no significant changes in cerebral cortex thickness or neuron intensity are observed

N • immunohistochemistry of the cortical region revealed that most signals of polyglutamylated tubulins remain in layer I as well as in the apical dendrites of cortical neurons in layer II/III

abnormal nervous system physiology ( J:345300 )

• brain lysates show a significant reduction in polyglutamylated beta-tubulins

• however, total amounts of both alpha- and beta-tubulins and other post-translational modifications (tubulin tyrosination and acetylation) are normal

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:345300 )

N • mice exhibit normal body temperature relative to wild-type controls

Genotype
MGI:7783462

cx2

• Allelic Composition: Ttll1^tm1Seto/Ttll1^tm1Seto; Ttll7^tm1Seto/Ttll7^tm1Seto
• Genetic Background: involves: 129 * 129S/SvEv * C57BL/6J

nervous system

nervous system phenotype ( J:345300 )

N • mice exhibit normal brain weight and whole-brain macroscopic morphology and coronal histology; no significant changes in cerebral cortex thickness or neuron intensity are observed

abnormal cerebral cortex morphology ( J:345300 )

• immunohistochemistry revealed that signals of polyglutamylated tubulins are abolished in layer I as well as in the apical dendrites of cortical neurons in layer II/III

• a tubulin co-sedimentation assay showed that several microtubule-associated proteins and motor proteins (CLIP170, MAP1A, dynein, and KIF1A) are strongly reduced

abnormal dendrite morphology ( J:345300 )

• apical dendrites of cortical neurons in layer II/III show a markedly decreased number of neurofilaments, resulting in a significantly reduced diameter (thickness) of axonal dendritic shafts

abnormal nervous system physiology ( J:345300 )

• brain lysates show a significant reduction in both polyglutamylated alpha-tubulins and beta-tubulins

• however, the total amount of both tubulins is almost unchanged

homeostasis/metabolism

increased gamma-aminobutyric acid level ( J:345300 )

• in sagittal sections, GABA levels are moderately increased in the brain cortex, hippocampal formation, and cerebellum regions

• in coronal sections, GABA levels are significantly increased in the cortex

increased glutamic acid level ( J:345300 )

• in sagittal sections, glutamate levels are significantly increased in the brain, esp. in the cortex, hippocampal formation, and cerebellum regions

• in coronal sections, glutamate levels are significantly increased in the cortex

increased glutamine level ( J:345300 )

• in sagittal sections, glutamine levels are slightly increased in the brain cortex and moderately increased in the cerebellum, but not significantly changed in the hippocampal formation region

• in coronal sections, glutamine levels are significantly increased in the cortex

increased isoleucine level ( J:345300 )

• in sagittal sections, leucine-isoleucine levels are moderately increased in the brain cortex and cerebellum and significantly increased in the hippocampal formation region

• in coronal sections, leucine-isoleucine levels are significantly increased in the cortex

increased leucine level ( J:345300 )

• in sagittal sections, leucine-isoleucine levels are moderately increased in the brain cortex and cerebellum and significantly increased in the hippocampal formation region

• in coronal sections, leucine-isoleucine levels are significantly increased in the cortex

increased valine level ( J:345300 )

• in sagittal sections, valine levels are significantly increased in the brain cortex, hippocampal formation, and cerebellum regions

• in coronal sections, valine levels are significantly increased in the cortex

Genotype
MGI:7783467

cx3

• Allelic Composition: Ttll1^tm1Seto/Ttll1⁺; Ttll7^tm1Seto/Ttll7^tm1Seto
• Genetic Background: involves: 129 * 129S/SvEv * C57BL/6J

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:345300 )

• following continuous i.p. injection of pilocarpine hydrochloride to induce kindling, mice show a significantly longer duration of obvious epilepsy-like symptoms (highest score) than wild-type controls over 135 min of observation

nervous system

increased susceptibility to pharmacologically induced seizures ( J:345300 )

• following continuous i.p. injection of pilocarpine hydrochloride to induce kindling, mice show a significantly longer duration of obvious epilepsy-like symptoms (highest score) than wild-type controls over 135 min of observation