Phenotypes Associated with This Genotype

Genotype
MGI:3785527

• Allelic Composition: Lep^ob/Lep^ob; Tg(Pomc-MAPT/Topaz)1Rck/0
• Genetic Background: involves: C57BL/6 * CBA

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

growth/size/body

decreased body weight ( J:90242 )

• treatment with 25 ug/g of leptin results in significant decrease in body weight in Lep^ob homozygotes compared to wild-type littermates

nervous system

abnormal neuron morphology ( J:90242 )

• Lep^ob homozygotes have a lower total number of synapses onto perikarya of Arcuate nucleus Pomc neurons compared to wild-type littermates; in wild-type, exciitory synapses on Pomc neurons are more numerous than inhibitory synapses, whereas in Lep^ob homozygotes, inhibitory synapses on Pomc neurons are more numerous

• altered synaptic profile is consistent with increased inhibitory tone on Pomc neurons in Lep^ob homozygotes

• 6 hours after leptin injection, an increase in total number of synapses on Pomc perikarya is detected, with an increase in excitatory inputs to Pomc cells; after 2 days of leptin treatment, synapse number onto Pomc neurons is doubled with a 300% increase in excitatory synapse number in Lep^ob homozygotes

• similar changes in synaptic profile are observed after 12 days of treatment

• after 4 days of twice-daily injections of 10 ug of ghrelin, number of excitatory inputs on Pomc neurons is decreased and number of inhibitory inputs is increased compared to saline-treated Lep mice (opposite to effect of leptin treatment)

abnormal inhibitory postsynaptic currents ( J:90242 )

• in Lep^ob homozygotes, there are 2-fold more inhibitory postsynaptic currents (IPSCs) as excitatory postsynaptic currents (EPSCs) onto Pomc neurons in the Arcuate nucleus in hypothalamic slices compared to wild-type mice

• 2 days of leptin treatment decreased frequency of spontaneous IPSCs onto Pomc neurons in Lep^ob homozygotes

behavior/neurological

decreased food intake ( J:90242 )

• treatment with 25 ug/g of leptin results in significant decrease in food intake after 2 and 12 days treatment

increased food intake ( J:90242 )

• after 4 days of twice-daily injections of 10 ug of ghrelin, an increase in food intake is observed