Phenotypes Associated with This Genotype

Genotype
MGI:7537119

• Allelic Composition: Saraf^{tm1c(KOMP)Wtsi}/Saraf^{tm1c(KOMP)Wtsi}; Tg(Pgk1-cre)1Lni/0
• Genetic Background: involves: 129S4/SvJaeSor * BALB/c * C57BL/6J * C57BL/6N
• Cell Lines: EPD0613_2_B07

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

growth/size/body

decreased lean body mass ( J:337869 )

• at 3 months and 1 year of age, percentage of lean mass is significantly lower than in control mice

increased susceptibility to age related obesity ( J:337869 )

• mice develop age-dependent sarcopenic obesity (not dependent on feeding or accompanied by diabetes)

increased body size ( J:337869 )

• at 1 year of age, mice are overtly larger than control mice

• however, linear growth is not altered

increased body weight ( J:337869 )

• at 3 months of age, body weight is on average ~10% more than that in control mice

• by 1 year of age, body weight is nearly 20% more than that in controls

adipose tissue

increased abdominal adipose tissue amount ( J:337869 )

• at 1 year of age, excess fat is distributed throughout the body with a high tendency for abdominal accumulation

whitened brown adipose tissue morphology ( J:337869 )

• fat accumulates in intracapsular brown adipose tissue (iBAT), resulting in iBAT whitening by 1 year of age

increased white fat cell size ( J:337869 )

• inguinal and visceral adipose tissues (iWAT and vWAT, respectively) show significant white fat cell hypertrophy at 3 months, with an upsurge noted at 1 year of age

increased percent body fat/body weight ( J:337869 )

• at 3 months and 1 year of age, percentage of fat mass is significantly higher than in control mice

liver/biliary system

increased susceptibility to age-related hepatic steatosis ( J:337869 )

• 1-year-old mice exhibit hepatic steatosis

• however, no fat accumulation is noted in the liver at 3 months of age

abnormal hepatocyte physiology ( J:337869 )

• primary hepatocytes isolated from 8- to 12-week-old mice show increased store-operated calcium entry (SOCE) activity, elevated Ca²⁺ oscillations in response to vasopressin (1 nM), and increased mitochondrial spare respiratory capacity

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:337869 )

N • at 3 months of age, mice exhibit normal fasting glucose levels and normal glucose tolerance relative to control mice

increased circulating corticosterone level ( J:337869 )

• after 15 min of restraint stress, blood corticosterone levels are significantly higher than in control mice, suggesting an increase in hypothalamus-pituitary-adrenal (HPA) axis activation

increased circulating thyroid-stimulating hormone level ( J:337869 )

• at 1 year of age, serum TSH levels are significantly higher than in control mice

abnormal calcium ion homeostasis ( J:337869 )

• primary hepatocytes show increased store-operated calcium entry (SOCE) activity, and elevated Ca²⁺ oscillations in response to physiological levels of vasopressin (1 nM)

decreased basal metabolism ( J:337869 )

• at 3 months of age, mice exhibit a lower metabolic rate, with significantly decreased heat production over time

cellular

decreased fibroblast proliferation ( J:337869 )

• primary mouse embryonic fibroblasts (MEFs) from E14.5 embryos show reduced proliferation relative to wild-type MEFs

decreased neuronal precursor proliferation ( J:337869 )

• in the dorsal and the ventral hippocampus dentate gyrus, the number of PCNA-positive cells per doublecortin (DCX)-positive neuronal progenitors is significantly lower than in control mice

abnormal cellular respiration ( J:337869 )

• primary hepatocytes exhibit an increased mitochondrial spare respiratory capacity

behavior/neurological

behavior/neurological phenotype ( J:337869 )

N • at 3 months of age, total food intake is not significantly altered, either under basal or refeed-challenged conditions

N • despite reduced neurogenesis, long-term memory (Morris water maze) and short-term memory (Y-maze) are unaffected

decreased anxiety-related response ( J:337869 )

• 3-month-old mice spend more time in the lit compartment in the dark-light transfer test and show a longer reaction time in the first of three blocks of 120-db stimuli in the acoustic startle response assay, indicating reduced anxiety-like behavior

decreased locomotor activity ( J:337869 )

• at 3 months of age, mice exhibit reduced dark-phase locomotion, as indicated by the light beam breaks count

nervous system

decreased neuronal precursor proliferation ( J:337869 )

• in the dorsal and the ventral hippocampus dentate gyrus, the number of PCNA-positive cells per doublecortin (DCX)-positive neuronal progenitors is significantly lower than in control mice

abnormal hippocampus physiology ( J:337869 )

• EdU incorporation assays show a significant decrease in proliferation in the dorsal and the ventral hippocampus dentate gyrus

endocrine/exocrine glands

decreased activity of thyroid gland ( J:337869 )

• at 1 year of age, mice exhibit subclinical hypothyroidism, with normal serum levels of thyroxine and cholesterol and increased serum TSH levels