Phenotypes Associated with This Genotype

Genotype
MGI:5297950

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Nts^tm1(cre)Mgmj/Nts⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB

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

growth/size/body

decreased lean body mass ( J:176657 )

• males have decreased lean mass as a proportion of body mass compared to controls at 12-15 weeks

abnormal body weight ( J:176657 )

• treatment with leptin for 24 hours reduces weight of control animals, but action of leptin is blunted in mutants

increased body weight ( J:176657 )

• at 12-15 weeks, mice show increased body weight relative to controls

adipose tissue

increased total body fat amount ( J:176657 )

• mice show higher adiposity at 12-15 weeks

increased gonadal fat pad weight ( J:176657 )

• gonadal fat pad white adipose tissue (WAT) weight is increased relative to controls at 12-15 weeks

abnormal percent body fat/body weight ( J:176657 )

• mice have increased % fat mass/total body mass compared to controls at 12-15 weeks

behavior/neurological

abnormal locomotor activation ( J:176657 )

• in response to injection of amphetamine (AMPH), locomotor activity rapidly increases in controls, but effect is blunted in Lepr mutants

decreased locomotor activity ( J:176657 )

• mice exhibit decreased ambulatory activity across the light-dark cycle compared to controls

nervous system

abnormal neuron physiology ( J:176657 )

• fasting does not increase activity of orexin neurons (measured by c-fos expression) in mutants in contrast to induction of robust activity in control animals

• treatment with leptin for 24 hours increases orexin expression by neurons in controls but not in mutants

abnormal synaptic dopamine release ( J:176657 )

• amphetamine-evoked dopamine release in the nucleus accumbens, NAc, is reduced (reduced amplitude of dopamine peak and increased dopamine biological half-life measured by amperometry) suggesting dopamine transporter activity is decreased in the NAc, contributing to reduceAMPH-induced activity

homeostasis/metabolism

increased circulating leptin level ( J:176657 )

• higher at 12-15 weeks

decreased oxygen consumption ( J:176657 )

• mice show decreased VO2 compared normalized to body weight compared to controls