All Phenotypes Gt(ROSA)26Sor<tm1.1(rtTA,tetO-cre)Bkmn> MGI Mouse

mortality/aging

premature death ( J:284745 )

• only a rare number of mice survive past 5 weeks after dox treatment, with some rare survivors living at least 100 days

• more than 50% of mice show prolonged survival after dox treatment in hypoxia compared to mice in normoxia which usually die 4 weeks after treatment

growth/size/body

increased body fat mass ( J:284745 )

• mice show increased fat body mass 2-3 weeks after dox treatment at 2-4 months of age

weight loss ( J:284745 )

• dox-treated mice exhibit weight loss

• the health crisis seen 4 weeks after dox treatment is preceded by a brief period of weight loss

• however, feeding is normal

behavior/neurological

impaired coordination ( J:284745 )

• mice show progressive decline in rotarod performance following dox-treatment

decreased grip strength ( J:284745 )

• mice show more than 50% reduction in forelimb grip strength at 25 days following termination of dox treatment

decreased vertical activity ( J:284745 )

• mice show decreased rearing shortly after dox-treatment

decreased locomotor activity ( J:284745 )

• mice show a decline in spontaneous motor and exploratory activity level as they become moribund at around 25 days post dox-treatment

• mice show reduced total activity and reduced day and night ambulation 2-3 weeks after dox treatment

homeostasis/metabolism

abnormal blood homeostasis ( J:284745 )

• serum succinate levels are elevated in dox-treated mice

• however, corticosteroid levels are unchanged following dox treatment

decreased circulating glucose level ( J:284745 )

• serum glucose levels are lower at 28 days following dox treatment

decreased circulating insulin level ( J:284745 )

• serum insulin levels are lower at 28 days following dox treatment

increased circulating creatine kinase level ( J:284745 )

• serum creatine kinase is elevated in dox-treated mice, indicating muscle damage

decreased energy expenditure ( J:284745 )

• mice show reduced resting, active, and total energy expenditure 2-3 weeks after dox treatment

lactic acidosis ( J:284745 )

• muscle lactate levels are increased in dox-treated mice indicating muscle lactic acidosis

adipose tissue

increased body fat mass ( J:284745 )

• mice show increased fat body mass 2-3 weeks after dox treatment at 2-4 months of age

cellular

abnormal tricarboxylic acid cycle ( J:284745 )

• mice treated with doxycycline (dox) show decreases in tricarboxylic acid cycle (TCA) metabolites citrate, isocitrate, and 2-ketoglutarate in muscle

• the succinate:2-ketoglutarate ratio is increased in tissues of dox-treated mice

muscle

abnormal muscle physiology ( J:284745 )

• muscle lactate levels are increased in dox-treated mice

• mice treated with doxycycline (dox) show decreases in tricarboxylic acid cycle (TCA) metabolites citrate, isocitrate, and 2-ketoglutarate in muscle

• however, serum lactate levels are not increased after dox treatment

neoplasm

neoplasm ( J:284745 )

N	• the few mice that live at least 100 days after dox treatment show no signs of paraganglioma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Leigh disease		DOID:3652	OMIM:256000	J:284745
NOT	paraganglioma	DOID:0050773	OMIM:115310 OMIM:168000 OMIM:601650 OMIM:605373 OMIM:614165 OMIM:PS168000	J:284745

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

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

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