Phenotypes associated with this allele

• Allele Symbol: Ttll1^tm1Seto
• Allele Name: targeted mutation 1, Mitsutoshi Setou
• Allele ID: MGI:4461777
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ttll1^tm1Seto/Ttll1^tm1Seto	B6.129-Ttll1^tm1Seto/SetoRbrc	MGI:7783457
hm2	Ttll1^tm1Seto/Ttll1^tm1Seto	involves: 129S/SvEv * C57BL/6	MGI:4461790
cx3	Ttll1^tm1Seto/Ttll1^tm1Seto Ttll7^tm1Seto/Ttll7^tm1Seto	involves: 129 * 129S/SvEv * C57BL/6J	MGI:7783462
cx4	Ttll1^tm1Seto/Ttll1^+ Ttll7^tm1Seto/Ttll7^tm1Seto	involves: 129 * 129S/SvEv * C57BL/6J	MGI:7783467

Genotype
MGI:7783457

hm1

• Allelic Composition: Ttll1^tm1Seto/Ttll1^tm1Seto
• Genetic Background: B6.129-Ttll1^tm1Seto/SetoRbrc

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

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

abnormal cerebral cortex morphology ( J:345300 )

• immunohistochemistry revealed that signals of polyglutamylated tubulins are markedly reduced in layer I but remain 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 alpha-tubulins

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

Genotype
MGI:4461790

hm2

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

respiratory system

abnormal respiratory motile cilium morphology ( J:161297 )

• mice exhibit loss of axonemal curvature in tracheal epithelial cilia compared with wild-type mice

• however, mice exhibit normal axonemes in tracheal epithelial cilia 9 + 2 structure

abnormal respiratory motile cilium physiology ( J:161297 )

• mice exhibit loss of beating asymmetry in isolated ATP-reactivated ciliary axonemes and intact tracheal ciliary axonemes compared with wild-type mice

• isolated and intact tracheal ciliary axonemes exhibit a 1.5-fold increase in ciliary beating frequency compared to in wild-type mice

rhinosinusitis ( J:161297 )

• mice exhibit an accumulation of mucous in the nasal cavity indicating rhinosinusitis compared with wild-type mice

abnormal tracheal ciliated epithelium morphology ( J:161297 )

• mice exhibit loss of axonemal curvature in tracheal epithelial cilia compared with wild-type mice

abnormal mucociliary clearance ( J:161297 )

• mice exhibit a decrease in cilia-driven transport compared with wild-type mice

• mice exhibit an accumulation of mucous in the nasal cavity indicating rhinosinusitis compared with wild-type mice

abnormal respiratory sounds ( J:161297 )

• mice exhibit coughing or sneezing-like noises unlike wild-type mice

coughing ( J:161297 )

• mice exhibit coughing-like noises

sneezing ( J:161297 )

• mice exhibit sneezing-like noises

immune system

rhinosinusitis ( J:161297 )

• mice exhibit an accumulation of mucous in the nasal cavity indicating rhinosinusitis compared with wild-type mice

reproductive system

short sperm flagellum ( J:161297 )

♂

cellular

abnormal respiratory motile cilium morphology ( J:161297 )

• mice exhibit loss of axonemal curvature in tracheal epithelial cilia compared with wild-type mice

• however, mice exhibit normal axonemes in tracheal epithelial cilia 9 + 2 structure

short sperm flagellum ( J:161297 )

♂

abnormal respiratory motile cilium physiology ( J:161297 )

• mice exhibit loss of beating asymmetry in isolated ATP-reactivated ciliary axonemes and intact tracheal ciliary axonemes compared with wild-type mice

• isolated and intact tracheal ciliary axonemes exhibit a 1.5-fold increase in ciliary beating frequency compared to in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary ciliary dyskinesia		DOID:9562	OMIM:PS244400	J:161297

Genotype
MGI:7783462

cx3

• 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

cx4

• 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