Phenotypes associated with this allele

• Allele Symbol: Snap25^tm1.1Bark
• Allele Name: targeted mutation 1.1, Christina Bark
• Allele ID: MGI:3821974
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Snap25^tm1.1Bark/Snap25^tm1.1Bark	B6.Cg-Snap25^tm1.1Bark	MGI:3821976
hm2	Snap25^tm1.1Bark/Snap25^tm1.1Bark	Not Specified	MGI:5766495

Genotype
MGI:3821976

hm1

• Allelic Composition: Snap25^tm1.1Bark/Snap25^tm1.1Bark
• Genetic Background: B6.Cg-Snap25^tm1.1Bark

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

behavior/neurological

abnormal spatial learning ( J:142096 )

• on days 2 and 4 of a Morris water maze test, mice exhibit a higher latency to navigate to the visible platform and longer swim distances compared to wild-type mice

• spatial learning deficits are more pronounced in female mice

increased anxiety-related response ( J:142096 )

• in an elevated plus maze, mice spend more time in closed arms than open arms compared to wild-type mice

increased thigmotaxis ( J:142096 )

• in a Morris water maze test

decreased locomotor activity ( J:142096 )

• mice exhibit reduced motility, locomotion and rearing compared to wild-type mice

seizures ( J:142096 )

• mice exhibit seizures but less frequently and at a later stage than those observed in Snap25^tm1Bark homozygotes

nervous system

seizures ( J:142096 )

• mice exhibit seizures but less frequently and at a later stage than those observed in Snap25^tm1Bark homozygotes

abnormal hippocampus CA3 region morphology ( J:142096 )

• in the stratum lucidum of CA3, 2 and 4 month old mice exhibit expanded mossy fibers that form large bundles and separate the synaptophysin+ nerve endings into island-like structures unlike in wild-type mice

• pathological changes are progressive with age

decreased paired-pulse facilitation ( J:142096 )

• at 0.2 Hz but not 0.5 Hz

growth/size/body

decreased body weight ( J:142096 )

• female mice weigh slightly less than wild-type mice

• however, male weights are normal

Genotype
MGI:5766495

hm2

• Allelic Composition: Snap25^tm1.1Bark/Snap25^tm1.1Bark
• Genetic Background: Not Specified

adipose tissue

increased white adipose tissue amount ( J:226064 )

• increase in amounts of mesenteric adipose tissue, peri-gonadal adipose tissue, retroperitoneal adipose tissue, and subcutaneous adipose tissue in mice fed the standard diet with a further increase on the Western diet, indicating central/abdominal obesity

increased white fat cell size ( J:226064 )

• mice on the standard diet exhibit enlarged adipose cell size in the subcutaneous and peri-gonadal adipose tissue

• a further increase in adipocyte cell size is seen on the Western diet

behavior/neurological

decreased food intake ( J:226064 )

♂ • average food and calorie intake of standard-diet fed males is lower than in wild-type mice

increased food intake ( J:226064 )

• average food and calorie intake of standard diet-fed females is increased compared to wild-type females

• average food and calorie intake of Western diet-fed males and females is increased compared to Western diet-fed wild-type mice

endocrine/exocrine glands

abnormal insulin secretion ( J:226064 )

• increase in pancreas insulin content in mice on a standard diet

growth/size/body

increased body mass index ( J:226064 )

• standard diet and Western diet-fed mice show increased body mass index

increased body weight ( J:226064 )

• standard diet-fed females show increased body weight around week 4 of the diet while males do at week 5 of the diet

increased susceptibility to diet-induced obesity ( J:226064 )

• high-fat/high-sucrose (Western) diet-fed mice show a dramatic increase in body weight, with significant increases in females after only 1 week and in males after 3 weeks of the diet

homeostasis/metabolism

abnormal insulin secretion ( J:226064 )

• increase in pancreas insulin content in mice on a standard diet

increased susceptibility to diet-induced obesity ( J:226064 )

• high-fat/high-sucrose (Western) diet-fed mice show a dramatic increase in body weight, with significant increases in females after only 1 week and in males after 3 weeks of the diet

hyperglycemia ( J:226064 )

• females exhibit an increase in basal blood glucose levels

• both primary (genetic) and secondary (dietary) preprandial hyperglycemia becomes significant after 3 weeks of diet intervention in males and at 6 weeks in females

decreased circulating ghrelin level ( J:226064 )

• standard diet-fed mice exhibit a decrease in basal serum ghrelin levels

increased circulating insulin level ( J:226064 )

♂ • males on a Western diet show an increase in basal serum insulin levels

increased circulating leptin level ( J:226064 )

• female, but not male, standard diet-fed mice show increased leptin levels

• Western diet-fed males and females show an 8-fold increase in basal leptin levels

increased circulating cholesterol level ( J:226064 )

• males fed the standard diet for 7 weeks exhibit higher blood cholesterol levels in week 3 of the diet while females do at week 4

• mice fed the Western diet exhibit severe increases in blood cholesterol levels

• preprandial blood cholesterol levels are increased

increased circulating triglyceride level ( J:226064 )

• males fed the standard diet for 7 weeks exhibit hypertriglyceridemia in week 5 of the diet while females do at week 3

• mice fed the Western diet exhibit severe hypertriglyceridemia

• preprandial blood triglyceride levels are increased

improved glucose tolerance ( J:226064 )

• mice fed a standard diet show lower blood glucose levels 15 min after glucose challenge

insulin resistance ( J:226064 )

♂ • males on the Western diet exhibit a severe inability to maintain normal blood glucose levels despite a 16-fold increase in insulin secretion during glucose tolerance testing, indicating insulin resistance

liver/biliary system

hepatic steatosis ( J:226064 )

• mice develop hepatic steatosis which progresses to severe fatty liver disease when mice are fed a Western diet

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:226064
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:226064