Phenotypes associated with this allele

• Allele Symbol: Lepr^tm1.1Chua
• Allele Name: targeted mutation 1.1 Streamson C Chua, Jr
• Allele ID: MGI:3511284
• Summary: 23 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lepr^tm1.1Chua/Lepr^tm1.1Chua	involves: 129 * C57BL/6	MGI:3511747
hm2	Lepr^tm1.1Chua/Lepr^tm1.1Chua	involves: 129 * C57BL/6J * FVB	MGI:3655812
cn3	Insr^tm1Khn/Insr^tm1Khn Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Pomc1-cre)16Lowl/0	involves: 129 * 129S4/SvJae * 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:5471586
cn4	Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Syn1-cre)671Jxm/0	involves: 129 * C57BL/6 * CBA	MGI:3837371
cn5	Lepr^tm1.1Chua/Lepr^+ Tg(Gh1-cre)bKnmn/0	involves: 129 * C57BL/6 * FVB	MGI:5014261
cn6	Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Gh1-cre)bKnmn/0	involves: 129 * C57BL/6 * FVB	MGI:5014260
cn7	Lepr^tm1.1Chua/Lepr^tm1.1Chua Prlh^tm1(cre)Smln/Prlh^+	involves: 129 * C57BL/6J	MGI:5634284
cn8	Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Nr5a1-cre)2Lowl/0 Tg(Pomc1-cre)16Lowl/0	involves: 129 * C57BL/6J * FVB	MGI:3663493
cn9	Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Nr5a1-cre)7Lowl/0	involves: 129 * C57BL/6J * FVB	MGI:3663485
cn10	Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Nr5a1-cre)2Lowl/0	involves: 129 * C57BL/6J * FVB	MGI:3663483
cn11	Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Pomc1-cre)16Lowl/0	involves: 129 * C57BL/6J * FVB	MGI:3640618
cn12	Lepr^tm1.1Chua/Lepr^tm1.1Chua Pgr^tm2(cre)Lyd/Pgr^+	involves: 129 * C57BL/6J * FVB/NJ	MGI:7278688
cn13	Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Pomc1-cre)16Lowl/0	involves: 129 * FVB	MGI:5142227
cn14	Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Pomc1-cre)16Lowl/0 Tg(Pomc1-hrGFP)1Lowl/0	involves: 129 * FVB	MGI:5142226
cn15	Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Agrp-cre)1Gsb/0	involves: 129 * FVB/N	MGI:5526038
cn16	Gt(ROSA)26Sor^tm2Sho/Gt(ROSA)26Sor^+ Lepr^tm1.1Chua/Lepr^tm1.1Chua Nts^tm1(cre)Mgmj/Nts^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * FVB/N	MGI:5297946
cn17	Lepr^tm1.1Chua/Lepr^tm1.2Chua Nos1^tm1(cre)Mgmj/Nos1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5319227
cn18	Lepr^tm1.1Chua/Lepr^tm1.1Chua Nts^tm1(cre)Mgmj/Nts^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB	MGI:5297950
cn19	Agrp^tm1(cre)Lowl/Agrp^+ Lepr^tm1.1Chua/Lepr^tm1.1Chua	involves: 129S6/SvEvTac	MGI:5142228
cn20	Lepr^tm1.1Chua/Lepr^tm1.1Chua Slc32a1^tm2(cre)Lowl/Slc32a1^+	involves: 129S6/SvEvTac	MGI:5142146
cn21	Lepr^tm1.1Chua/Lepr^tm1.1Chua Slc17a6^tm2(cre)Lowl/Slc17a6^+	involves: 129S6/SvEvTac	MGI:5142145
cn22	Lepr^tm1.1Chua/Lepr^tm1.1Chua Slc32a1^tm2(cre)Lowl/Slc32a1^+ Tg(Pomc1-hrGFP)1Lowl/0	involves: 129S6/SvEvTac * FVB/N	MGI:5142225
cn23	Agrp^tm1(cre)Lowl/Agrp^+ Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Pomc1-hrGFP)1Lowl/0	involves: 129S6/SvEvTac * FVB/N	MGI:5142229

Genotype
MGI:3511747

hm1

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua
• Genetic Background: involves: 129 * C57BL/6

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

Obesity in Lepr^tm1Chua/Lepr^tm1Chua mice (center) and normal weight in Lepr^tm1.1Chua/Lepr^tm1.1Chua (left)

growth/size/body

growth/size/body region phenotype ( J:94019 )

N • body weight not significantly different from normal controls

homeostasis/metabolism

decreased circulating glucose level ( J:94019 )

• serum glucose levels in females reduced about 12.9%, serum values otherwise normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:94019

Genotype
MGI:3655812

hm2

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua
• Genetic Background: involves: 129 * C57BL/6J * FVB

normal phenotype

no abnormal phenotype detected ( J:106354 )

• homozygotes have identical body weights to wild-type littermates

Genotype
MGI:5471586

cn3

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Pomc1-cre)16Lowl/0
• Genetic Background: involves: 129 * 129S4/SvJae * 129S6/SvEvTac * C57BL/6J * FVB/N

adipose tissue

increased abdominal adipose tissue amount ( J:192274 )

♀ • trend towards increased intra-abdominal adiposity at 4 months of age

increased fat cell size ( J:192274 )

♀ • perigonadal adipocyte hypertrophy at 4 months of age

abnormal gonadal fat pad morphology ( J:192274 )

♀ • perigonadal adipocyte hypertrophy at 4 months of age

♀ • an increase in macrophage accumulation is seen in the perigonadal fat indicating inflammation

increased percent body fat/body weight ( J:192274 )

♀ • percent body fat is increased in females at 4 months of age, however absolute body weight is not increased at this time

white adipose tissue inflammation ( J:192274 )

♀ • an increase in macrophage accumulation is seen in the perigonadal fat, and macrophage marker analysis and cytokine expression indicates low-grade inflammation in adipose tissue

endocrine/exocrine glands

absent corpus luteum ( J:192274 )

♀ • 45% of mice lack either corpora lutea or preovulatory follicles

absent mature ovarian follicles ( J:192274 )

♀ • 45% of mice lack either corpora lutea or preovulatory follicles

ovary inflammation ( J:192274 )

♀ • low-grade inflammation as indicated by increased IL-6 expression in the ovary

growth/size/body

decreased lean body mass ( J:192274 )

♀ • percent lean body mass is decreased at 4 months of age

homeostasis/metabolism

hyperglycemia ( J:192274 )

♀ • females are hyperglycemic before (at 3 months of age) and during pregnancy (at gestational days 12 and 15), without evidence of gestational glucose intolerance

increased circulating leptin level ( J:192274 )

♀ • circulating levels of adipokine leptin are increased at 4 months of age

immune system

white adipose tissue inflammation ( J:192274 )

♀ • an increase in macrophage accumulation is seen in the perigonadal fat, and macrophage marker analysis and cytokine expression indicates low-grade inflammation in adipose tissue

ovary inflammation ( J:192274 )

♀ • low-grade inflammation as indicated by increased IL-6 expression in the ovary

liver inflammation ( J:192274 )

♀ • low-grade inflammation as indicated by increased IL-1beta expression in the liver

liver/biliary system

liver inflammation ( J:192274 )

♀ • low-grade inflammation as indicated by increased IL-1beta expression in the liver

reproductive system

absent corpus luteum ( J:192274 )

♀ • 45% of mice lack either corpora lutea or preovulatory follicles

absent mature ovarian follicles ( J:192274 )

♀ • 45% of mice lack either corpora lutea or preovulatory follicles

ovary inflammation ( J:192274 )

♀ • low-grade inflammation as indicated by increased IL-6 expression in the ovary

decreased ovulation rate ( J:192274 )

♀ • females exhibit reduced ovulation but show normal cycling suppression from fasting

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
polycystic ovary syndrome		DOID:11612	OMIM:184700	J:192274

Genotype
MGI:3837371

cn4

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Syn1-cre)671Jxm/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

homeostasis/metabolism

increased insulin secretion ( J:145998 )

decreased circulating adrenaline level ( J:145998 )

decreased circulating noradrenaline level ( J:145998 )

endocrine/exocrine glands

increased insulin secretion ( J:145998 )

nervous system

abnormal sympathetic nervous system physiology ( J:145998 )

• sympathetic tone, as measured by Ucp1 expression and levels of epinephrine and norepinephrine, is low compared to in wild-type mice

• however, treatment with isoproterenol increases sympathetic tone

Genotype
MGI:5014261

cn5

• Allelic Composition: Lepr^tm1.1Chua/Lepr⁺; Tg(Gh1-cre)bKnmn/0
• Genetic Background: involves: 129 * C57BL/6 * FVB

endocrine/exocrine glands

decreased somatotroph cell number ( J:173444 )

• in F1 generation males, a significant decrease in growth hormone-positive somatrophs is observed

nervous system

decreased somatotroph cell number ( J:173444 )

• in F1 generation males, a significant decrease in growth hormone-positive somatrophs is observed

reproductive system

reproductive system phenotype ( J:173444 )

N • mice are fertile

Genotype
MGI:5014260

cn6

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Gh1-cre)bKnmn/0
• Genetic Background: involves: 129 * C57BL/6 * FVB

mortality/aging

lethality, incomplete penetrance ( J:173444 )

• litters from F3 generation mutant dams are smaller than those from cre-negative dams or mutants from the F1or F2 generations; litter size of female mutants of the F1 or F2 generations conform to the expected size

growth/size/body

increased lean body mass ( J:173444 )

• 10 month-old F3 females show a significant increase in lean body mass; 3.5 month-old males and females and 10 month-old males do not exhibit any increase

increased body weight ( J:173444 )

• growth rates are identical to controls up to 3 months of age but mean body weights for F3 generation males and females diverge from controls at 4 and 6.5 months, respectively

• at 9 months, F3 females are 46% heavier than controls but after 9 months, females lose weight with the average weight no longer being different from controls; males are significantly heavier than controls by 4 months of age with the difference continuing throughout life (at least 12-13 months)

obese ( J:173444 )

• F3 male mutants develop obesity with age

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:173444 )

N • serum leptin and insulin levels are not different from controls in 3-4 month-old F3 males or females (all young adult groups even if group contained obese animals); no changes are observed in serum Igf1 levels

increased circulating leptin level ( J:173444 )

• leptin levels rise with obesity in older male and female mutants

decreased circulating growth hormone level ( J:173444 )

• levels are reduced by 72% in F3 generation adult males and by 50% in F3 female adults

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:173444 )

N • despite reduction in GH-positive somatotroph numbers, there is no change in overall number of pituitary cells, or changes in pituitary size or morphology

decreased somatotroph cell number ( J:173444 )

• in F2 and F3 generation male and female mice, there is a significant decrease in growth hormone-positive cells

adipose tissue

increased total body fat amount ( J:173444 )

• some F3 generation animals were analyzed by DEXA (dual-energy x-ray absorptiometry) to look for changes in fat and lean mass

• 3.5 month-old F3 males show signficantl increases in grams of body fat; females show significant increases in fat mass at 3.5 and (in a small subset) at 10 months

nervous system

decreased somatotroph cell number ( J:173444 )

• in F2 and F3 generation male and female mice, there is a significant decrease in growth hormone-positive cells

reproductive system

reproductive system phenotype ( J:173444 )

N • timing of puberty is normal in mutants

Genotype
MGI:5634284

cn7

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Prlh^tm1(cre)Smln/Prlh⁺
• Genetic Background: involves: 129 * C57BL/6J

homeostasis/metabolism

increased circulating insulin level ( J:215557 )

• at 16 weeks

increased circulating leptin level ( J:215557 )

• at 16, but not 6, weeks

decreased core body temperature ( J:215557 )

• slightly over a 24 hour period

abnormal body temperature homeostasis ( J:215557 )

• at 6 weeks, mice treated with leptin fails to increase core body temperature unlike wild-type mice

decreased energy expenditure ( J:215557 )

decreased oxygen consumption ( J:215557 )

• at 8 to 10 weeks

abnormal response/metabolism to endogenous compounds ( J:215557 )

• at 6 weeks, mice treated with leptin fails to increase core body temperature unlike wild-type mice

• at 6 weeks, mice treated with leptin fail to exhibit an increase core body temperature and exhibit an attenuated reduction in night-time feeding compared with wild-type mice

• however, mice respond to the satiating effect of Cck normally

growth/size/body

increased body weight ( J:215557 )

• at 16 weeks

obese ( J:215557 )

• late-onset at 16 weeks

adipose tissue

increased subcutaneous adipose tissue amount ( J:215557 )

• at 16 weeks

increased epididymal fat pad weight ( J:215557 )

• at 16 weeks

behavior/neurological

behavior/neurological phenotype ( J:215557 )

N • mice exhibit normal food intake and respond to the satiating effect of Cck normally

integument

increased subcutaneous adipose tissue amount ( J:215557 )

• at 16 weeks

Genotype
MGI:3663493

cn8

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Nr5a1-cre)2Lowl/0; Tg(Pomc1-cre)16Lowl/0
• Genetic Background: involves: 129 * C57BL/6J * FVB

adipose tissue

increased total body fat amount ( J:105327 )

• increase in fat mass

abnormal fat pad morphology ( J:105327 )

• size of fat pads (perigonadal, perirenal, and mesenteric) is increased

abnormal gonadal fat pad morphology ( J:105327 )

abnormal mesenteric fat pad morphology ( J:105327 )

abnormal renal fat pad morphology ( J:105327 )

growth/size/body

obese ( J:105327 )

• weigh significantly more than mice lacking Lepr only in SF1 neurons or POM1 neurons

homeostasis/metabolism

increased circulating leptin level ( J:105327 )

Genotype
MGI:3663485

cn9

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Nr5a1-cre)7Lowl/0
• Genetic Background: involves: 129 * C57BL/6J * FVB

growth/size/body

increased body weight ( J:105327 )

• degree of obesity is about 20% of that seen in homozygous Lepr^tm1.2Chua mice

Genotype
MGI:3663483

cn10

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Nr5a1-cre)2Lowl/0
• Genetic Background: involves: 129 * C57BL/6J * FVB

adipose tissue

increased total body fat amount ( J:105327 )

• increase in fat mass but no difference in lean mass

abnormal fat pad morphology ( J:105327 )

• size of fat pads (perigonadal and perirenal) is increased

abnormal gonadal fat pad morphology ( J:105327 )

• size of perigonadal fat pads is increased

abnormal renal fat pad morphology ( J:105327 )

• size of perirenal fat pads is increased

growth/size/body

increased body weight ( J:105327 )

• 15% increase in body weight at 20 weeks of age compared to controls; degree of obesity is about 20% of that seen in homozygous Lepr^tm1.2Chua mice

increased susceptibility to diet-induced obesity ( J:105327 )

• rapidly gain weight when fed a high-fat diet compared to controls; weight gain is reflected by increases in fat mass

• when switch from a regular chow to a high-fat diet at 8 weeks of age, mutants gain substantially greater amounts of weight than controls

homeostasis/metabolism

increased circulating leptin level ( J:105327 )

abnormal energy expenditure ( J:105327 )

• show marked impairment in ability to activate diet-induced thermogenesis in response to a high-fat diet

increased susceptibility to diet-induced obesity ( J:105327 )

• rapidly gain weight when fed a high-fat diet compared to controls; weight gain is reflected by increases in fat mass

• when switch from a regular chow to a high-fat diet at 8 weeks of age, mutants gain substantially greater amounts of weight than controls

nervous system

abnormal nervous system electrophysiology ( J:105327 )

• leptin has no effect on either membrane potential or firing rate of neurons unlike in controls which show depolarization and increased firing rate in response to leptin

behavior/neurological

increased food intake ( J:105327 )

• fail to suppress food intake over time when fed a high fat diet

Genotype
MGI:3640618

cn11

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Pomc1-cre)16Lowl/0
• Genetic Background: involves: 129 * C57BL/6J * FVB

growth/size/body

increased body weight ( J:105327 )

obese ( J:106354 )

• exhibit mild obesity with an increase in body weight at 10 weeks of age that is 18.2% that of homozygous Lepr^tm1.2Chua mice

adipose tissue

increased total body fat amount ( J:105327 , J:106354 )

• increase in fat mass (J:105327)

• exhibit increased body fat but no differences in food intake or energy expenditure (J:106354)

abnormal fat pad morphology ( J:105327 , J:106354 )

abnormal epididymal fat pad morphology ( J:106354 )

• epididymal fat pads are at least twice as large as in controls

abnormal gonadal fat pad morphology ( J:105327 )

• size of perigonadal fat pads is increased

abnormal mesenteric fat pad morphology ( J:105327 , J:106354 )

• size of mesenteric fat pads is increased (J:105327)

• mesenteric fat pads are at least twice as large as in controls (J:106354)

abnormal renal fat pad morphology ( J:105327 , J:106354 )

• size of perirenal fat pads is increased (J:105327)

• perirenal fat pads are at least twice as large as in controls (J:106354)

homeostasis/metabolism

increased circulating leptin level ( J:105327 , J:106354 )

Genotype
MGI:7278688

cn12

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129 * C57BL/6J * FVB/NJ

reproductive system

reproductive system phenotype ( J:324160 )

♀N • virgin females exhibited normal estrous cycle length in days relative to control females

abnormal embryo implantation ( J:324160 )

♀ • at day 6.5 of pregnancy, the ratio of viable implantation sites to corpora lutea was significantly lower than in controls, suggesting reduced implantation efficiency

♀ • however, no significant differences are observed in the average number of implantation sites or corpora lutea at day 6.5 of pregnancy

abnormal parturition ( J:324160 )

♀ • dams exhibited a high incidence of stillbirth and dystocia, indicating labor dysfunction

♀ • however, pregnancy was normal at day 17.5, as determined by maternal weight, fetal weight, number of live fetuses, number of resorption sites, and placental weight and structure

delayed parturition ( J:324160 )

♀ • with increasing parity, dams took increasingly longer than controls to produce pups after being placed with a proven breeder male

♀ • by their 4th parity, dams took significantly more time from pairing to delivery than controls

♀ • 2 of 12 dams failed to produce a 4th litter by the end of the breeding trial (90 days after pairing)

♀ • average time from crouching to delivery of each pup was significantly increased relative to controls

♀ • very long labor times were observed in a few individuals

♀ • however, no postpartum cervical histological differences were observed

dystocia ( J:324160 )

♀ • 2 additional females had to be euthanized for dystocia in the first parity

♀ • over 4 parities, 34% of deliveries resulted in either dystocia, stillbirth or both, whereas no adverse outcomes were seen in control dams

♀ • overall, females delivered significantly more stillborn pups than controls; some dead pups appeared constricted or squeezed (flattened)

♀ • 12.5% of pregnancies ended in dystocia

reduced female fertility ( J:324160 )

♀ • the total number of live pups born to dams after 4 parities was 22% lower than in controls

decreased litter size ( J:324160 )

♀ • the number of pups per litter was significantly lower than in control dams independent of parity

behavior/neurological

pup cannibalization ( J:324160 )

♀ • in some cases, only pieces of stillborn pups were observed, likely due to maternal cannibalism

embryo

embryo phenotype ( J:324160 )

♀N • at day 17.5 of pregnancy, dams showed no structural anomalies, size differences or signs of inflammation or hemorrhage in the placenta relative to controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:324160 )

♀N • serum progesterone concentrations were normal at day 3.5 of pregnancy

Genotype
MGI:5142227

cn13

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Pomc1-cre)16Lowl/0
• Genetic Background: involves: 129 * FVB

nervous system

nervous system phenotype ( J:174691 )

N • no change in spontaneous IPSC amplitude or frequency in Pomc1 neurons in slices is observed, indicating that Lepr deletion from postsynaptic Pomc1 neurons does not affect inhibitory tone

Genotype
MGI:5142226

cn14

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Pomc1-cre)16Lowl/0; Tg(Pomc1-hrGFP)1Lowl/0
• Genetic Background: involves: 129 * FVB

nervous system

nervous system phenotype ( J:174691 )

N • addtion of leptin to neurons reduces the frequency of spontaneous (s)IPSCs in Pomc1 neurons by about 40%, similar to the inhibition observed in control neurons

Genotype
MGI:5526038

cn15

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Agrp-cre)1Gsb/0
• Genetic Background: involves: 129 * FVB/N

homeostasis/metabolism

decreased liver triglyceride level ( J:199803 )

• blunting of the increase in liver triglycerides during fasting

liver/biliary system

decreased liver triglyceride level ( J:199803 )

• blunting of the increase in liver triglycerides during fasting

Genotype
MGI:5297946

cn16

• Allelic Composition: Gt(ROSA)26Sor^tm2Sho/Gt(ROSA)26Sor⁺; Lepr^tm1.1Chua/Lepr^tm1.1Chua; Nts^tm1(cre)Mgmj/Nts⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * FVB/N

nervous system

abnormal nervous system electrophysiology ( J:176657 )

• all lateral hypothalamic area (LHA) Nts +ve neurons treated with leptin become hyperpolarized; in controls, about 20% of wild-type LHA Nts +ve neurons treated with leptin while about 60% depolarize upon leptin treatment

• this indicates that deletion of Lepr from Lepr, Nts +ve neurons abrogates the direct depolarization response

Genotype
MGI:5319227

cn17

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.2Chua; Nos1^tm1(cre)Mgmj/Nos1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

growth/size/body

increased body weight ( J:183754 )

• males have higher body weight relative to controls from 4-12 weeks similar to males with whole-body deletion of Lepr (Lepr^tm1.2Chua/ Lepr^tm1.2Chua; Nos1^tm1(cre)Mgmj/ Nos⁺ males)

• females display weight increase, but it is less severe than in females with whole-body deletion of Lepr

homeostasis/metabolism

decreased circulating thyroxine level ( J:183754 )

• levels of T4 are lower in males compared to controls; these levels are higher than in males with whole-body deletion of Lepr

increased circulating glucose level ( J:183754 )

• higher than controls from weaning age on in males and females

increased circulating corticosterone level ( J:183754 )

• circulating corticosterone levels in males are similar to controls

increased circulating insulin level ( J:183754 )

increased circulating leptin level ( J:183754 )

• starting at weaning age (8 weeks), much higher than controls at 8 weeks in males and females

decreased oxygen consumption ( J:183754 )

• males show decreased maximal oxygen consumption relative to controls at 12-14 weeks; oxygen consumption is similar to complete Lepr knockout males

adipose tissue

increased total body fat amount ( J:183754 )

• males have higher amount of adipose tissue similar to males with whole-body deletion of Lepr

behavior/neurological

behavior/neurological phenotype ( J:183754 )

N • circulating corticosterone levels are similar to controls

increased food intake ( J:183754 )

• from 4-12 weeks, males show increased food intake relative to controls similar to males with whole-body deletion of Lepr

• females display increased food consumption, but it is less severe than in females with whole-body deletion of Lepr

decreased locomotor activity ( J:183754 )

• at 12-14 weeks, males show decreased ambulatory activity in both dark and light cycles in 24-hour period

• females show decreased ambulatory activity during the light cycle

reproductive system

reproductive system phenotype ( J:183754 )

N • timing of litter delivery is similar to controls (24 days vs. 23 days in controls) and litter sizes are similar to controls

delayed estrous cycle ( J:183754 )

♀ • onset of vaginal estrous is delayed relative to controls in singly housed females

Genotype
MGI:5297950

cn18

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

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

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

decreased response to leptin ( J:176657 )

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

Genotype
MGI:5142228

cn19

• Allelic Composition: Agrp^tm1(cre)Lowl/Agrp⁺; Lepr^tm1.1Chua/Lepr^tm1.1Chua
• Genetic Background: involves: 129S6/SvEvTac

nervous system

nervous system phenotype ( J:174691 )

N • no change in spontaneous IPSC amplitude or frequency is observed in Pomc1 neurons in slices

Genotype
MGI:5142146

cn20

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Slc32a1^tm2(cre)Lowl/Slc32a1⁺
• Genetic Background: involves: 129S6/SvEvTac

growth/size/body

increased body weight ( J:174691 )

• males and females exhibit a massive increase in body weight from 4 weeks of age through 7 weeks compared to controls

behavior/neurological

polyphagia ( J:174691 )

• food intake is greatly increased compared to controls

nervous system

abnormal nervous system electrophysiology ( J:174691 )

• Pomc1 neurons tend to be hyperpolarized relative to control neurons

abnormal inhibitory postsynaptic currents ( J:174691 )

• a large increase in amplitude and frequency of spontaneous IPSCs is observed in Pomc1 neurons in slice preparations from mice with conditional deletion of Lepr, indicating that deletion from presynaptic GABAergic neurons increases the inhibitory tone in Pomc1 neurons

homeostasis/metabolism

abnormal circulating glucose level ( J:174691 )

• animals have significantly elevated fed and fasting blood glucose levels

increased circulating insulin level ( J:174691 )

• animals have significantly elevated fed and fasted serum insulin levels

adipose tissue

increased total body fat amount ( J:174691 )

• animals display a massive increase in fat mass relative to controls at 10 weeks of age

Genotype
MGI:5142145

cn21

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Slc17a6^tm2(cre)Lowl/Slc17a6⁺
• Genetic Background: involves: 129S6/SvEvTac

growth/size/body

growth/size/body region phenotype ( J:174691 )

N • animals do not show significant changes in body weight up to 11 weeks of age

behavior/neurological

behavior/neurological phenotype ( J:174691 )

N • food intake shows no significant difference compared to controls

nervous system

nervous system phenotype ( J:174691 )

N • deletion of Lepr in Slc17a6 neurons does not alter IPSC amplitude in Agrp neurons; IPSC frequency is decreased (not significantly) in Agrp

N • excitatory postsynaptic currents (sEPSCs and mEPSCs) in Pomc1 neurons are not affected by Lepr deletion in Slc17a6 (glutamatergic) neurons

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:174691 )

N • fed and fasted blood glucose levels are unchanged and serum insulin levels are only slightly increased in the fed state

adipose tissue

adipose tissue phenotype ( J:174691 )

N • no increase in fat mass is observed at 10 weeks

Genotype
MGI:5142225

cn22

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Slc32a1^tm2(cre)Lowl/Slc32a1⁺; Tg(Pomc1-hrGFP)1Lowl/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

nervous system

abnormal inhibitory postsynaptic currents ( J:174691 )

• addition of leptin fails to reduce the frequency of sIPSCs (spontaneous inhibitory postsynaptic currents) in Pomc1 neurons, while in control slices, the frequency is reduced by about 40%

Genotype
MGI:5142229

cn23

• Allelic Composition: Agrp^tm1(cre)Lowl/Agrp⁺; Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Pomc1-hrGFP)1Lowl/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

nervous system

nervous system phenotype ( J:174691 )

N • addition of leptin produces similar inhibition of sIPSCs in neurons to that observed in control preparations