Phenotypes associated with this allele

• Allele Symbol: Vti1b^tm1Gfvm
• Allele Name: targeted mutation 1, Gabriele Fischer von Mollard
• Allele ID: MGI:2670119
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Vti1b^tm1Gfvm/Vti1b^tm1Gfvm	involves: 129P2/OlaHsd * C57BL/6J	MGI:2670123
cx2	Vti1a^tm1Gfvm/Vti1a^tm1Gfvm Vti1b^tm1Gfvm/Vti1b^tm1Gfvm	involves: 129P2/OlaHsd * C57BL/6	MGI:4940039

Genotype
MGI:2670123

hm1

• Allelic Composition: Vti1b^tm1Gfvm/Vti1b^tm1Gfvm
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

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

mortality/aging

premature death ( J:84574 )

• a few of the smaller homozygotes die between 3 and 5 weeks of age

growth/size/body

enlarged gallbladder ( J:84574 )

• 18% of smaller homozygotes display an enlarged gall bladder

decreased body weight ( J:84574 )

• although all homozygotes display normal weight gain until P16 to P18, 22% (two-thirds of them males) lose weight and remain significantly lighter thereafter

• however, the remaining homozygotes grow at rates similar to those of heterozygous or wild-type littermates

liver cyst ( J:84574 )

• 35% of normal-size homozygotes older than 15 months exhibit multiple liver cysts

• liver cysts were filled with a clear fluid, except for two small cysts containing a yellow liquid

liver/biliary system

enlarged gallbladder ( J:84574 )

• 18% of smaller homozygotes display an enlarged gall bladder

liver cyst ( J:84574 )

• 35% of normal-size homozygotes older than 15 months exhibit multiple liver cysts

• liver cysts were filled with a clear fluid, except for two small cysts containing a yellow liquid

gallstones ( J:84574 )

• gallstones were observed in one of the smaller homozygotes

abnormal hepatocyte morphology ( J:84574 )

• 2 of 16 smaller homozygotes contain large amounts of PAS-positive globules, identified as glycogen, in their hepatocytes

• hepatocytes of some (2 of 3) smaller homozygotes display marked accumulation of both early and late autophagic vacuoles and multivesicular bodies

• more multivesicular endosomes and autophagic vacuoles are in close contact with each other or appear to be in the process of fusion

• in contrast, hepatocytes derived from normal-size homozygotes are indistinguishable from wild-type hepatocytes

cellular

abnormal lysosome physiology ( J:84574 )

• hepatocytes derived from smaller homozygotes exhibit a slight delay in lysosomal delivery and degradation of endocytosed 125I-asialofetuin

• however, no difference in degradation of 125I-asialofetuin is observed between hepatocytes from wild-type and normal-size homozygous mutant mice

• in addition, mutant hepatocytes degrade long-lived proteins at wild-type rates, suggesting that autophagic protein degradation is unaffected

endocrine/exocrine glands

enlarged gallbladder ( J:84574 )

• 18% of smaller homozygotes display an enlarged gall bladder

Genotype
MGI:4940039

cx2

• Allelic Composition: Vti1a^tm1Gfvm/Vti1a^tm1Gfvm; Vti1b^tm1Gfvm/Vti1b^tm1Gfvm
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

perinatal lethality, complete penetrance ( J:169107 )

• mice die at birth

nervous system

increased neuron apoptosis ( J:169107 )

• in the trigeminal ganglia

abnormal superior cervical ganglion morphology ( J:169107 )

• superior cervical ganglia fail to innervate the mandibular gland unlike in wild-type mice

decreased brain size ( J:169107 )

enlarged brain ventricles ( J:169107 )

• wider at E14.5 and E18.5

enlarged lateral ventricles ( J:169107 )

abnormal brain commissure morphology ( J:169107 )

• major projection tracts and commissures are absent or reduced in size compared to in wild-type mice

• however, midline glia development is normal

decreased corpus callosum size ( J:169107 )

• in the anteroposterior extent and thickness

absent hippocampal commissure ( J:169107 )

• E18.5, the hippocampal commissure and fibers of fornix are missing unlike in wild-type mice

absent anterior commissure ( J:169107 )

abnormal optic tract morphology ( J:169107 )

• diminished

abnormal striatum morphology ( J:169107 )

• at E18.5, mice exhibit an unusual bundle of fibers, consisting of corticostriatal and thamacocortical axons, on the lateral side of the striatum unlike in wild-type mice

abnormal innervation ( J:169107 )

• superior cervical ganglia fail to innervate the mandibular gland unlike in wild-type mice

abnormal nervous system development ( J:169107 )

abnormal axon extension ( J:169107 )

• dorsal root ganglia explants exposed to NGF exhibit fewer and shorter neurites compared with similarly treated wild-type explants

abnormal axon guidance ( J:169107 )

• at E14.5, thalamocortical axons do not cross the pallio-subpallial border unlike in wild-type mice

• at E18.5, thalamocortical axons fail to reach the cortex and remain within the internal capsule region unlike in wild-type mice

• numerous fiber tracts in the central nervous system are missing, reduced in size, or misrouted compared to in wild-type mice

abnormal cranial ganglia morphology ( J:169107 )

small petrosal ganglion ( J:169107 )

• at E14.5

vestibular ganglion hypoplasia ( J:169107 )

• mild at E14.5

vestibular ganglion degeneration ( J:169107 )

• mild

decreased optic chiasm size ( J:169107 )

• diminished

abnormal sensory ganglion morphology ( J:169107 )

small geniculate ganglion ( J:169107 )

small trigeminal ganglion ( J:169107 )

• beginning at E12.5 and worsening with age

small nodose ganglion ( J:169107 )

• at E14.5

dorsal root ganglion degeneration ( J:169107 )

• at E14.5 and worsening with age

neurodegeneration ( J:169107 )

• progressive in the peripheral nervous system (severe in the trigeminal, nodose, petrosal, geniculate, and dorsal root ganglia; moderate in the superior cervical ganglia; mild in the vestibular and cochlear ganglia)

cellular

cellular phenotype ( J:169107 )

N • cells exhibit normal plasma membrane, early and late endosomes, and lysosomes

increased neuron apoptosis ( J:169107 )

• in the trigeminal ganglia

abnormal axon extension ( J:169107 )

• dorsal root ganglia explants exposed to NGF exhibit fewer and shorter neurites compared with similarly treated wild-type explants

abnormal axon guidance ( J:169107 )

• at E14.5, thalamocortical axons do not cross the pallio-subpallial border unlike in wild-type mice

• at E18.5, thalamocortical axons fail to reach the cortex and remain within the internal capsule region unlike in wild-type mice

• numerous fiber tracts in the central nervous system are missing, reduced in size, or misrouted compared to in wild-type mice

vision/eye

decreased optic chiasm size ( J:169107 )

• diminished