Phenotypes Associated with This Genotype

Genotype
MGI:2670123

• 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