Phenotypes Associated with This Genotype

Genotype
MGI:3785526

• Allelic Composition: Lep^ob/Lep^ob; Tg(Npy-MAPT/Sapphire)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 saline-treated mice

nervous system

nervous system phenotype ( J:90242 )

N • after 4 days of twice-daily injections of 10 ug of ghrelin, no differences in excitatory or inhibitory synapse number are detected relative to saline-treated mice

abnormal neuron morphology ( J:90242 )

• Lep^ob homozygotes have significantly more synapses onto perikarya of Arcuate nucleus Npy neurons compared to wild-type littermates; in wild-type, inhibitory synapses onto Npy neurons are more numerous than excitatory synapses, whereas in Lep^ob homozygotes, excitatory synapses onto Npy neurons are more numerous

• altered synaptic profile is consistent with increased excitatory tone onto Npy neurons in Lep^ob homozygotes

• 6 hours after leptin injection, a reduction in total number of synapses on Npy perikarya is detected, with a decrease in excitatory inputs and increased inhibitory inputs to Npy cells; after 2 days of leptin treatment, synapse number onto Npy neurons is significantly decreased with a 6-fold reduction decrease in excitatory synapse number and a 2-fold increase in inhibitory synapse number in Lep^ob homozygotes

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

abnormal excitatory postsynaptic currents ( J:90242 )

• a significantly higher number of spontaneous EPSCs (sEPSCs) onto Npy neurons in hypothalamic slices from Lep^ob homozygotes is observed compared to Npy neurons in wild-type mice; this is accompanied by a reduction in frequency of sIPSCs relative to wild-type controls

• a tendency toward a decrease in spontaneous EPSC number onto Npy neurons is observed 2 days of leptin treatment 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