Phenotypes associated with this allele

• Allele Symbol: Tg(tetO-Xbp1_is)#Pesch
• Allele Name: transgene insertion, Philipp E Scherer
• Allele ID: MGI:6376136
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cad^tm1c(KOMP)Wtsi/Cad^tm1c(KOMP)Wtsi Tg(Adipoq-rtTA)2Zvw/0 Tg(tetO-cre)1Jaw/0 Tg(tetO-Xbp1_is)#Pesch/0	involves: 129 * C57BL/6 * C57BL/6N * FVB/N	MGI:6376231
cn2	Gt(ROSA)26Sor^tm1(rtTA,EGFP)Nagy/Gt(ROSA)26Sor^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tg(tetO-Xbp1_is)#Pesch/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA * FVB	MGI:6376140
cx3	Tg(tetO-Xbp1_is)#Pesch/0 Tg(Adipoq-rtTA)2Zvw/0	involves: C57BL/6 * C57BL/6N * FVB/N	MGI:6376191
cx4	Lep^ob/Lep^ob Tg(tetO-Xbp1_is)#Pesch/0 Tg(Adipoq-rtTA)2Zvw/0	involves: C57BL/6 * C57BL/6N * FVB/N	MGI:6376200

Genotype
MGI:6376231

cn1

• Allelic Composition: Cad^{tm1c(KOMP)Wtsi}/Cad^{tm1c(KOMP)Wtsi}; Tg(Adipoq-rtTA)2Zvw/0; Tg(tetO-cre)1Jaw/0; Tg(tetO-Xbp1_is)#Pesch/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6N * FVB/N
• Cell Lines: EPD0282_2_F10

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

growth/size/body

weight loss ( J:260830 )

• mice continue to increase their body weight when switched to a doxycycline (Dox)-containing diet, although not at the same extent as wild-type mice thus showing a partial reversal of weight loss

adipose tissue

adipose tissue phenotype ( J:260830 )

N • size of adipocytes is epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (sWAT), and in interscapular brown adipose tissue (BAT)is normal in Dox-treated mice

N • adipose tissue uridine content is not increased and thus rescued in Dox-treated mice compared to Tg(tetO-Xbp1_is)#Pesch/0 Tg(Adipoq-rtTA)2Zvw/0 mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:260830 )

N • adipose tissue uridine content is not increased and thus rescued in Dox-treated mice compared to Tg(tetO-Xbp1_is)#Pesch/0 Tg(Adipoq-rtTA)2Zvw/0 mice

Genotype
MGI:6376140

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tg(tetO-Xbp1_is)#Pesch/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA * FVB

adipose tissue

decreased total body fat amount ( J:194290 )

• doxycycline (Dox)-treated mice show a gradual reduction in the volume of adipose tissue

• when mice are taken off the Dox-containing diet, the fat tissue volume increases

homeostasis/metabolism

increased circulating free fatty acids level ( J:194290 )

• increase in serum free fatty acids in the fed state after 72 hours of induction with Dox

• however, Dox-treated mice maintain the same rate of fatty acid and cholesterol synthesis as controls in a biochemical assay for de novo lipid synthesis

increased respiratory quotient ( J:194290 )

• mice fed a doxycycline (Dox)-containing diet show a higher respiratory exchange ratio than wild-type mice during the dark phase

abnormal glucose homeostasis ( J:194290 )

• mice exhibit a reduction in hepatic glucose release when exposed to Dox for 48 hours

• metabolic cage studies indicate higher glucose utilization in Dox-treated mice

decreased fasting circulating glucose level ( J:194290 )

• a 6-hour fast causes severe hypoglycemia within 48 hours after induction with Dox

hypoglycemia ( J:194290 )

• serum glucose levels start to decrease by 72 hours after induction with Dox under fed conditions

• administration of a PPAR-alpha agonist exacerbates the hypoglycemia in Dox-treated mice

decreased circulating insulin level ( J:194290 )

• fed insulin levels start to decrease upon induction with Dox and are significantly lower by 72 hours of induction

• 96 hours after Dox-induction, fasted insulin levels are lower

decreased liver glycogen level ( J:194290 )

• hepatic glycogen is severely depleted after 48 hours of induction with Dox

increased insulin sensitivity ( J:194290 )

• livers of Dox-treated mice show a faster response to insulin exposure and isolated hepatocytes induced with Dox show an enhanced insulin response indicating hepatic insulin sensitivity

increased liver triglyceride level ( J:194290 )

• hepatic triglyceride content is increased in Dox-treated mice

• a 6-hour fast increases liver triglyceride content acutely within 24 hours of Dox exposure

enhanced lipolysis ( J:194290 )

• the fasting effects of adipocyte lipolysis on hepatic triglyceride content are exacerbated in Dox-treated mice compared to wild-type mice

liver/biliary system

abnormal liver morphology ( J:194290 )

• liver mass is increased 1.7-fold within 48 hours of induction with Dox

• Dox-treated mice show reduced dry mass content per wet liver

• increase in total liver protein in Dox-treated mice

decreased liver glycogen level ( J:194290 )

• hepatic glycogen is severely depleted after 48 hours of induction with Dox

increased liver triglyceride level ( J:194290 )

• hepatic triglyceride content is increased in Dox-treated mice

• a 6-hour fast increases liver triglyceride content acutely within 24 hours of Dox exposure

hepatic steatosis ( J:194290 )

• Dox-treated mice show an increase in hepatic lipid levels

• when mice are taken off the Dox-containing diet, the liver steatosis decreases rapidly

Genotype
MGI:6376191

cx3

• Allelic Composition: Tg(tetO-Xbp1_is)#Pesch/0; Tg(Adipoq-rtTA)2Zvw/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * FVB/N

growth/size/body

decreased body fat mass ( J:260830 )

• weight loss in doxycycline (Dox)-treated mice is mainly due to a reduction of fat mass

weight loss ( J:260830 )

• mice start to lose body weight immediately upon switching to Dox-containing diet

decreased susceptibility to diet-induced obesity ( J:260830 )

• Dox-treated mice fed a high-fat diet show a decrease in body weight and lower overall adiposity compared to wild-type mice

homeostasis/metabolism

increased fatty acid oxidation ( J:260830 )

• 6 days after the switch to Dox chow, fatty acid oxidation rates are elevated in sWAT

• 90 days after the switch to Dox chow, fatty acid oxidation rates are elevated in both sWAT and BAT

• however, lipid uptake rates are normal

• however, fatty acid or ketone bodies in circulation upon fasting are not affected in Dox-treated mice

decreased susceptibility to diet-induced obesity ( J:260830 )

• Dox-treated mice fed a high-fat diet show a decrease in body weight and lower overall adiposity compared to wild-type mice

decreased body temperature ( J:260830 )

• mice maintain their body temperature slightly but significantly lower than wild-type mice by day 10 of Dox exposure

• however, Dox-treated mice show no difference in food intake

increased carbon dioxide production ( J:260830 )

• mice exhibit higher rates of carbon dioxide release under fed, fasted, and refed conditions within 10 days after the switch to Dox chow

increased oxygen consumption ( J:260830 )

• mice exhibit higher rates of oxygen consumption under fed, fasted, and refed conditions within 10 days after the switch to Dox chow

increased basal metabolism ( J:260830 )

• mice exhibit higher rates of oxygen consumption and carbon dioxide release under fed, fasted, and refed conditions within 10 days after the switch to Dox chow, indicating increased metabolic rate

• heat production is higher under all conditions tested in Dox-treated mice

abnormal nucleotide metabolism ( J:260830 )

• upon induction with doxycycline (Dox), mice increase plasma uridine levels 2-fold and maintain elevated levels as long as they are kept on Dox

• Dox-treated mice exhibit higher uridine concentrations in epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (sWAT), and in interscapular brown adipose tissue (BAT)

• adipocytes grown in culture in the presence of Dox show an initial consumption of uridine by the cells similarly to wild-type cells but subsequently show a greater net release of uridine into the culture medium than wild-type cells

• suppression of uridine release by PALA, an inhibitor of de novo pyrimidine synthesis, is abolished in mature adipocytes

adipose tissue

decreased body fat mass ( J:260830 )

• weight loss in doxycycline (Dox)-treated mice is mainly due to a reduction of fat mass

decreased brown adipose tissue mass ( J:260830 )

• smaller BAT weight in Dox-treated mice

decreased fat cell size ( J:260830 )

• adipocyte size is reduced in Dox-treated mice

abnormal white adipose tissue morphology ( J:260830 )

• Dox-treated mice exhibit less fibrosis and inflammation in eWAT at 40 weeks of age

decreased white adipose tissue mass ( J:260830 )

• smaller WAT weight in Dox-treated mice

cellular

increased fatty acid oxidation ( J:260830 )

• 6 days after the switch to Dox chow, fatty acid oxidation rates are elevated in sWAT

• 90 days after the switch to Dox chow, fatty acid oxidation rates are elevated in both sWAT and BAT

• however, lipid uptake rates are normal

• however, fatty acid or ketone bodies in circulation upon fasting are not affected in Dox-treated mice

Genotype
MGI:6376200

cx4

• Allelic Composition: Lep^ob/Lep^ob; Tg(tetO-Xbp1_is)#Pesch/0; Tg(Adipoq-rtTA)2Zvw/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * FVB/N

growth/size/body

decreased susceptibility to diet-induced obesity ( J:260830 )

• doxycycline (Dox)-treated mice fed a high-fat diet show a slower weight gain compared to single Lep^ob homozygous mice but do not show an actual net weight loss

• Dox-treated mice fed a high-fat diet show a reduction in fat mass gain compared to Lep^ob homozygous mice

homeostasis/metabolism

decreased susceptibility to diet-induced obesity ( J:260830 )

• doxycycline (Dox)-treated mice fed a high-fat diet show a slower weight gain compared to single Lep^ob homozygous mice but do not show an actual net weight loss

• Dox-treated mice fed a high-fat diet show a reduction in fat mass gain compared to Lep^ob homozygous mice