Phenotypes Associated with This Genotype

Genotype
MGI:2654709

hm14

• Allelic Composition: Lep^ob/Lep^ob
• Genetic Background: involves: C57BL/6J

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

liver/biliary system

increased liver weight ( J:219118 )

hepatic steatosis ( J:219118 )

growth/size/body

increased heart weight ( J:116841 )

• heart weight elevated relative to controls

increased lean body mass ( J:219118 )

• increase in lean mass at 8 and 16 weeks of age

obese ( J:92558 , J:219118 )

• increase in weight gain in a short period of time (J:219118)

increased body length ( J:219118 )

abnormal postnatal growth ( J:6236 )

• pair fed mice restrict food intake to that of controls

• pair fed mice gain less weight as protein than when feeding is unrestricted

• pair fed mice gain considerably more weight as fat than controls eating the same quantity of food

• pair fed mice gain less weight than when feeding is unrestricted

increased liver weight ( J:219118 )

endocrine/exocrine glands

abnormal colon goblet cell morphology ( J:109110 )

• increased number of mucus filled goblet cells in the colon

enlarged pancreatic islets ( J:219118 )

• increase in the size of islets of Langerhans and appearance of enormous islets in the pancreas of 30 week old mice

abnormal insulin secretion ( J:14402 , J:22634 )

• lower threshold for glucose induced insulin secretion by beta cells (J:14402)

• acetyl choline has a greater affect to lower the glucose induced threshold for insulin secretion (J:22634)

mortality/aging

postnatal lethality, incomplete penetrance ( J:219118 )

♂ • 50 % higher postnatal death rate of males

homeostasis/metabolism

abnormal glucose homeostasis ( J:92558 )

abnormal insulin secretion ( J:14402 , J:22634 )

• lower threshold for glucose induced insulin secretion by beta cells (J:14402)

• acetyl choline has a greater affect to lower the glucose induced threshold for insulin secretion (J:22634)

increased fasting circulating glucose level ( J:219118 )

• fasting mice show increased glucose levels at 6 weeks of age

hyperglycemia ( J:92558 , J:219118 )

impaired glucose tolerance ( J:86303 , J:219118 )

• observed prior to any significant increase in body weight (J:86303)

insulin resistance ( J:219118 )

• in the insulin tolerance test, mice reduce their glucose levels within 30 min to about 80% compared to 50% in wild-type mice at 6 weeks of age

• mice do not respond to insulin in the insulin tolerance test at 15 weeks of age, indicating insulin resistance

abnormal hormone level ( J:13151 )

increased circulating insulin level ( J:92558 )

abnormal corticosterone level ( J:13151 )

• corticosterone response to stress greater than in controls

• diurnal variation greater than in controls

increased circulating corticosterone level ( J:60001 )

• severe

increased adrenocorticotropin level ( J:13151 )

• levels in the pituitary are much higher than in pituitaries of controls

skeleton

increased bone mass ( J:60001 )

• denser vertebrae and long bones at 6 months

• increased bone mass even on a low fat diet to delay obesity

osteopetrosis ( J:60001 )

• increased numbers of thick trabeculae at 3 and 6 months

• 2 fold increase in trabecular bone volume

abnormal skeleton development ( J:60001 )

• rate of new bone formation increased at both 3 and 6 months

abnormal osteoclast differentiation ( J:60001 )

• increased numbers of osteoclasts

hematopoietic system

abnormal osteoclast differentiation ( J:60001 )

• increased numbers of osteoclasts

adipose tissue

increased fat cell size ( J:5765 , J:219118 )

• increase in area size of epigonadal fat cells (J:219118)

increased gonadal fat pad weight ( J:219118 )

• increase in epigonadal fat tissue weight

increased inguinal fat pad weight ( J:219118 )

increased interscapular fat pad weight ( J:219118 )

increased percent body fat/body weight ( J:219118 )

• increase in fat mass at 8 and 16 weeks of age

digestive/alimentary system

abnormal intestinal mucosa morphology ( J:109110 )

• thick mucus gel covers the epithelium of the colon

abnormal colon goblet cell morphology ( J:109110 )

• increased number of mucus filled goblet cells in the colon

cardiovascular system

abnormal retina vasculature morphology ( J:92072 )

• neovascularization is significantly suppressed under standard oxygen conditions relative to controls

increased heart weight ( J:116841 )

• heart weight elevated relative to controls

abnormal cardiovascular system physiology ( J:116841 )

• attenuated heart response to increased calcium

• oxygen consumption of the heart does not increase with an increased workload

• oxygen consumption is elevated when perfused with glucose and palmitate

muscle

abnormal muscle contractility ( J:106205 )

• number of tetani required to reduce force by 40% is significantly less than for controls

• basal calcium ion concentration increases sharply toward the end of a series of 50 tetanic contractions (single cell measures)

vision/eye

abnormal retina vasculature morphology ( J:92072 )

• neovascularization is significantly suppressed under standard oxygen conditions relative to controls

nervous system

decreased nerve conduction velocity ( J:121015 )

• 16% lower motor nerve conduction velocity than controls

• hind limb sensory nerve conduction velocity reduced 22%

behavior/neurological

abnormal behavior ( J:112820 )

• faster in food finding trials relative to controls

polyphagia ( J:219118 )

• mice eat twice as much as wild-type mice

decreased locomotor activity ( J:219118 )

increased thermal nociceptive threshold ( J:121015 )

• 88% increased latency of hind-limb withdrawal from a heat stimulus

immune system

abnormal osteoclast differentiation ( J:60001 )

• increased numbers of osteoclasts

cellular

abnormal colon goblet cell morphology ( J:109110 )

• increased number of mucus filled goblet cells in the colon

abnormal osteoclast differentiation ( J:60001 )

• increased numbers of osteoclasts

abnormal respiratory electron transport chain ( J:116841 )

• mitochondrial respiration is inhibited in glucose perfused hearts

• increased ADP dependent mitochondrial respiration in glucose and palmitate perfused hearts

• mitochondrial respiration is uncoupled in glucose and palmitate perfused hearts

integument

abnormal epidermal layer morphology ( J:121015 )

• significant reduction in intraepidermal nerve fiber density

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
abdominal obesity-metabolic syndrome 1		DOID:14221	OMIM:605552	J:219118