Phenotypes associated with this allele

• Allele Symbol: Ttbk2^tm1Dral
• Allele Name: targeted mutation 1, Dario R Alessi
• Allele ID: MGI:5056320
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ttbk2^tm1Dral/Ttbk2^tm1Dral	involves: C57BL/6	MGI:5056321
ht2	Ttbk2^tm1Dral/Ttbk2^+	involves: C57BL/6	MGI:6305408
ht3	Ttbk2^bby/Ttbk2^tm1Dral	involves: C57BL/6	MGI:6305409
ht4	Ttbk2^tm1Dral/Ttbk2^tm1a(EUCOMM)Hmgu	involves: C57BL/6 * C57BL/6N	MGI:6305412

Genotype
MGI:5056321

hm1

• Allelic Composition: Ttbk2^tm1Dral/Ttbk2^tm1Dral
• Genetic Background: involves: C57BL/6

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

mortality/aging

preweaning lethality, complete penetrance ( J:173629 )

• despite normal Mendelian ratios at E10, no mice are produced

cardiovascular system

abnormal direction of heart looping ( J:269515 )

• E10.5 embryos exhibit a randomized heart laterality

cellular

absent embryonic cilia ( J:269515 )

• embryos lack cilia in mesenchymal cells surrounding the neural tube

• embryos do not form any cilia

abnormal cell physiology ( J:269515 )

• mouse embryonic fibroblasts fail to recruit IFT proteins to the basal body and retain the cilium-suppressing centrosomal protein CP110 at the distal mother centriole

embryo

absent embryonic cilia ( J:269515 )

• embryos lack cilia in mesenchymal cells surrounding the neural tube

• embryos do not form any cilia

incomplete embryo turning ( J:173629 )

embryonic growth retardation ( J:173629 )

• at E10

decreased embryo size ( J:173629 )

• at E10

nervous system

abnormal nervous system development ( J:269515 )

• embryos exhibit neural patterning defects, including the absence of NKX2.2+ V3 interneuron progenitors and ISL1+ motor neurons that are shifted ventrally to span the midline

abnormal brain development ( J:173629 )

• at E10, brains lack prominent subdivisions unlike in wild-type mice

abnormal cranial flexure morphology ( J:269515 )

• E10.5 embryos exhibit a pointed midbrain flexure

holoprosencephaly ( J:269515 )

• E10.5 embryos exhibit holoprosencephaly

growth/size/body

embryonic growth retardation ( J:173629 )

• at E10

decreased embryo size ( J:173629 )

• at E10

Genotype
MGI:6305408

ht2

• Allelic Composition: Ttbk2^tm1Dral/Ttbk2⁺
• Genetic Background: involves: C57BL/6

nervous system

nervous system phenotype ( J:269515 )

N • cerebellar architecture at 3 months of age is normal

Genotype
MGI:6305409

ht3

• Allelic Composition: Ttbk2^bby/Ttbk2^tm1Dral
• Genetic Background: involves: C57BL/6

cellular

absent embryonic cilia ( J:269515 )

• embryos do not form any cilia

embryo

absent embryonic cilia ( J:269515 )

• embryos do not form any cilia

Genotype
MGI:6305412

ht4

• Allelic Composition: Ttbk2^tm1Dral/Ttbk2^{tm1a(EUCOMM)Hmgu}
• Genetic Background: involves: C57BL/6 * C57BL/6N
• Cell Lines: HEPD0767_5_E08

mortality/aging

prenatal lethality, incomplete penetrance ( J:269515 )

• only 9.5% of pups instead of the expected 25% of pups are recovered at birth, suggesting some prenatal lethality

embryo

abnormal neural tube morphology ( J:269515 )

• structure of cilia in neural tube sections from E10.5 embryos is abnormal, with microtubules appearing less distinct, with the proximal cilium/transition zone having a less organized appearance, and vesicles within the ciliary axonemes

cellular

abnormal cilium morphology ( J:269515 )

• mouse embryonic fibroblasts (MEFs) show fewer cells that are ciliated compared

• mean cilia length is reduced in MEFs

• treatment of MEFs with nocodazole results in a rapid reduction in ciliated cells and the length of remaining cilia reduces over time compared to wild-type MEFs which show a slight decrease, indicating that cilium stability is compromised

limbs/digits/tail

polydactyly ( J:269515 )

• fully penetrant polydactyly on all 4 limbs at E15.5

nervous system

abnormal nervous system development ( J:269515 )

• E10.5 embryos show defects in neural patterning, with the ISL1+ motor neuron domain shifted ventrally and ISL1+ cells at the ventral midline, an extensive intermixing of OLIG2+ and NKX2.2+ progenitor populations, and OLIG2+ cells that are often found at the ventral midline

abnormal neural tube morphology ( J:269515 )

• structure of cilia in neural tube sections from E10.5 embryos is abnormal, with microtubules appearing less distinct, with the proximal cilium/transition zone having a less organized appearance, and vesicles within the ciliary axonemes