Phenotypes Associated with This Genotype

Genotype
MGI:4429407

• Allelic Composition: Lep^ob/Lep^ob
• Genetic Background: involves: STOCK Mlph^ln a Tgfa^wa1 Cdh23^v Ednrb^s

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

growth/size/body

increased body weight ( J:159285 )

decreased body length ( J:13066 )

• first noticeable at 4-6 weeks of age

• short body

• square shape

• expansive hind quarters

increased growth rate ( J:13066 )

• begin to gain weight rapidly by 4-6 weeks of age

• weigh twice as much as controls at 3 months of age

• weigh 75-90g at 10 months

liver/biliary system

decreased liver triglyceride level ( J:199803 )

• lower level than wild-type after 36 hour fasting in 7-week-old mice.

increased liver triglyceride level ( J:199803 )

• double the control littermate's triglyceride level in 7 to 14 weeks old mice

decreased susceptibility to hepatic steatosis ( J:199803 )

• after 36 hour fasting in 7-week-old mice

behavior/neurological

polyphagia ( J:7702 )

• hyperphagia

homeostasis/metabolism

abnormal response to cardiac infarction ( J:219470 )

• mice exhibit a significant decline in cardiac function, and increase in apoptosis and necrosis, and elevated reactive oxygen species generation after myocardial ischemia/reperfusion injury

abnormal vascular wound healing ( J:135034 )

• reduced neointimal area relative to controls 4 weeks after femoral artery injury

• neointimal area increased by leptin injection or adenoviral leptin treatment

• vascular smooth muscle proliferation significantly reduced

impaired adaptive thermogenesis ( J:7702 , J:12010 )

• extreme cold susceptibility (J:7702)

• mice moved directly to 4C from 21C become hypothermic and die (J:7702)

• mice acclimated to 12C before exposure survive better to 4C exposure than un-acclimated controls (J:7702)

• 60 minute exposure of 17 day old mice to 4C results in a marked drop in body temperature (J:12010)

decreased circulating tumor necrosis factor level ( J:115569 )

• 48% of control levels after kainate injection

decreased body temperature ( J:12010 )

• mice have a lower basal body temperature than controls

abnormal glucose homeostasis ( J:7702 )

hyperglycemia ( J:7702 )

• transient hyperglycemia

impaired glucose tolerance ( J:7702 )

abnormal hormone level ( J:7702 )

• increased beta endorphin levels

• increased levels of melanocyte stimulating hormone

increased circulating insulin level ( J:7702 )

increased adrenocorticotropin level ( J:7702 )

• increased pituitary ACTH

decreased liver triglyceride level ( J:199803 )

• lower level than wild-type after 36 hour fasting in 7-week-old mice.

increased liver triglyceride level ( J:199803 )

• double the control littermate's triglyceride level in 7 to 14 weeks old mice

abnormal nucleotide metabolism ( J:260830 )

• subcutaneous white adipose tissue (sWAT) has less uridine content than in wild-type mice

• however, epididymal white adipose tissue (eWAT) and liver uridine content are not different

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:7702 )

increased pancreatic beta cell mass ( J:7702 )

• increased size

increased pancreatic beta cell number ( J:7702 )

abnormal gland physiology ( J:7702 )

hypersecretion of corticosterone ( J:7702 )

• increased glucocorticoids from the adrenal

decreased activity of thyroid gland ( J:7702 )

adipose tissue

abnormal fat cell morphology ( J:5253 , J:7702 )

• hyperplasia (J:7702)

increased fat cell size ( J:7702 )

abnormal white adipose tissue morphology ( J:260830 )

• subcutaneous white adipose tissue (sWAT) has less uridine content than in wild-type mice

skeleton

abnormal long bone epiphyseal plate morphology ( J:102535 )

• more fragile than controls

• failure at a force of 4.9 Newtons as compared to 8.4 Newtons in controls

• breakage at the chondro-osseous junction

• reduced expression of "type-X" collagen

• less organized loose reticular distribution of collagen fibrils

abnormal long bone epiphyseal plate proliferative zone ( J:102535 )

• column structure is disturbed

• poor alignment

abnormal long bone hypertrophic chondrocyte zone ( J:102535 )

• column structure is disturbed

• poor alignment

• mostly mineralized as compared to less than 50% mineralized in controls

• increased numbers of apoptotic chondrocytes

decreased length of long bones ( J:102535 )

short humerus ( J:102535 )

short femur ( J:102535 )

decreased bone mass ( J:7702 )

• reduced bone mass

reproductive system

infertility ( J:7702 )

female infertility ( J:7702 )

♀ • homozygous females fail to ovulate

male infertility ( J:7702 )

♂ • all older males are sterile

reduced male fertility ( J:7702 )

♂ • only 20% of young males are fertile

nervous system

abnormal embryonic neuroepithelium morphology ( J:105139 )

• significantly fewer cells at E16 and E18 but not at E14

• cell proliferation is lower at E14 and E16

decreased embryonic neuroepithelium thickness ( J:105139 )

• thin at E18

abnormal microglial cell physiology ( J:115569 )

• 30-40% as many activated microglia 5 days after kainic acid treatment as for controls

• migrate normally to injury sites but do not proliferate

abnormal cortical plate morphology ( J:105139 )

• fewer cells in the cortical plate at E18

decreased embryonic neuroepithelial cell proliferation ( J:105139 )

• cell proliferation is lower at E14 and E16

cardiovascular system

abnormal arteriole morphology ( J:151096 )

• basal arteriolar diameter is greater than controls

• potassium-ATP channel inhibition eliminates diameter difference from controls

abnormal response to cardiac infarction ( J:219470 )

• mice exhibit a significant decline in cardiac function, and increase in apoptosis and necrosis, and elevated reactive oxygen species generation after myocardial ischemia/reperfusion injury

abnormal vascular wound healing ( J:135034 )

• reduced neointimal area relative to controls 4 weeks after femoral artery injury

• neointimal area increased by leptin injection or adenoviral leptin treatment

• vascular smooth muscle proliferation significantly reduced

immune system

abnormal microglial cell physiology ( J:115569 )

• 30-40% as many activated microglia 5 days after kainic acid treatment as for controls

• migrate normally to injury sites but do not proliferate

decreased circulating tumor necrosis factor level ( J:115569 )

• 48% of control levels after kainate injection

limbs/digits/tail

short humerus ( J:102535 )

short femur ( J:102535 )

embryo

abnormal embryonic neuroepithelium morphology ( J:105139 )

• significantly fewer cells at E16 and E18 but not at E14

• cell proliferation is lower at E14 and E16

decreased embryonic neuroepithelium thickness ( J:105139 )

• thin at E18

hematopoietic system

abnormal microglial cell physiology ( J:115569 )

• 30-40% as many activated microglia 5 days after kainic acid treatment as for controls

• migrate normally to injury sites but do not proliferate

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
abdominal obesity-metabolic syndrome		DOID:0060611	OMIM:PS605552	J:219470