Phenotypes associated with this allele

• Allele Symbol: Sim1⁺
• Allele Name: wild type
• Allele ID: MGI:2436018
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Sim1^tm1Fan/Sim1^+	involves: 129/Sv * C57BL/6	MGI:3036852
ht2	Sim1^tm1.1Az/Sim1^+	involves: 129X1/SvJ * C57BL/6 * FVB	MGI:3527276
ht3	Sim1^Rgsc646/Sim1^+	involves: C57BL/6JJcl * DBA/2JJcl	MGI:3812150
cn4	Sim1^tm1.1(cre)Gld/Sim1^+ Tg(CAG-Bgeo,-AlstR,-EGFP)192Gld/0	involves: 129S1/Sv * C57BL/6 * SJL	MGI:3839918
cn5	Gt(ROSA)26Sor^tm2(GFP/tetX)Gld/Gt(ROSA)26Sor^+ Sim1^tm1.1(cre)Gld/Sim1^+	involves: C57BL/6 * SJL	MGI:3839917
cx6	Sim1^tm1Fan/Sim1^+ Sim2^tm1Fan/Sim2^tm1Fan	involves: 129S1/Sv * 129X1/SvJ	MGI:3613782
cx7	Sim1^tm1Fan/Sim1^+ Sim2^tm1Fan/Sim2^+	involves: 129/Sv * C57BL/6	MGI:3036853

Genotype
MGI:3036852

ht1

• Allelic Composition: Sim1^tm1Fan/Sim1⁺
• Genetic Background: involves: 129/Sv * C57BL/6

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

adipose tissue

abnormal brown adipose tissue morphology ( J:70586 )

• cells are larger

increased brown adipose tissue amount ( J:70586 )

• mass of brown fat was increased

abnormal white adipose tissue morphology ( J:70586 )

• white adipose tissue cells are histologically normal

increased white adipose tissue amount ( J:70586 )

• increased mass of white fat due to increased number of cells

behavior/neurological

polyphagia ( J:70586 )

• food intake increased around 4-5 weeks of age

• hyperphagia persists over time

growth/size/body

increased body length ( J:70586 )

• heterozygotes have a greater naso-anal length after 4 weeks than do controls

increased susceptibility to weight gain ( J:70586 )

• while growth is normal until 4 weeks of age, weight gain after that time is elevated in both males and females

homeostasis/metabolism

abnormal glucose homeostasis ( J:70586 )

• blood glucose levels were normal at 8 and 24 weeks of age

increased circulating insulin level ( J:70586 )

• although normal at 8 weeks, insulin levels were significantly elevated by 24 weeks of age

• while growth is normal until 4 weeks of age, weight gain after that time is elevated in both males and females

nervous system

abnormal diencephalon morphology ( J:50772 )

• paraventricular nucleus and supraoptic nuclei are hypocellular

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:70586

Genotype
MGI:3527276

ht2

• Allelic Composition: Sim1^tm1.1Az/Sim1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * FVB

adipose tissue

increased total body fat amount ( J:95410 )

• percent body fat was increased, with females more severely affected

behavior/neurological

polyphagia ( J:95410 )

• on a low fat diet, consumed 14% more food per day than controls

• on a high fat diet, males consumed 46% more than controls

• three- to fourfold increase in the percent difference in food intake of heterozyogotes versus controls fed the high versus the low fat diet

growth/size/body

increased body weight ( J:95410 )

• males had more than twice as much fat mass as controls and females had more than tree times as much

• lean mass of both males and females was increased by more than 20%

obese ( J:95410 )

• 8 week old females weighed 13% and 71% more than controls fed a low fat and high fat diet, respectively

• 8 week old males weighed 22% and 51% more than controls fed a low fat and high fat diet, respectively

• continued to gain weight until more than 6 months of age on the low fat diet and 4 months of age on the high fat diet

increased body length ( J:95410 )

• heterozygotes fed either a low or high fat diet were longer than wild-type

increased susceptibility to diet-induced obesity ( J:95410 )

• males consumed 46% more food on a high fat diet than controls and became obese

homeostasis/metabolism

increased circulating glucose level ( J:95410 )

• female, but not male, heterozygotes weaned onto the high fat diet had slightly increased serum glucose levels compared to controls, however no differences in glucose levels on the low fat diet

increased circulating insulin level ( J:95410 )

• heterozygotes weaned on the low fat diet had higher serum insulin levels, however young (6-8 week old) mice had normal levels

increased circulating leptin level ( J:95410 )

• serum leptin levels were elevated in both males and females fed the low fat diet

abnormal energy homeostasis ( J:95410 )

• heterozygous males had 2.5 or 1.9-fold greater feeding efficiency (weight gained per kilocalorie ingested) than controls fed the low fat or high fat diet, respectively

• heterozygous females had 2 or 3-fold greater feeding efficiency than controls fed the low fat or high fat diet, respectively

• increased energy consumption by 57% (males) or 49% (females) when shifted from low fat to high fat diet compared to a 20% increase in controls

increased susceptibility to diet-induced obesity ( J:95410 )

• males consumed 46% more food on a high fat diet than controls and became obese

Genotype
MGI:3812150

ht3

• Allelic Composition: Sim1^Rgsc646/Sim1⁺
• Genetic Background: involves: C57BL/6JJcl * DBA/2JJcl

growth/size/body

obese ( J:133634 )

• mice with this mutation are significantly heavier than normal at 8 and 12 weeks; at 17 weeks, the male founder mouse weighed 57.6 g

hematopoietic system

increased glycosylated hemoglobin level ( J:133634 )

• elevated HbA1c was reported in progeny of the founder mouse at 11 and 16 weeks of age

homeostasis/metabolism

increased glycosylated hemoglobin level ( J:133634 )

• elevated HbA1c was reported in progeny of the founder mouse at 11 and 16 weeks of age

hyperglycemia ( J:133634 )

• at 19 weeks of age, the founder mouse had a serum glucose level of 541.5 mg/dL; hyperglycemia was reported in progeny of the founder mouse at 11 and 16 weeks

increased circulating insulin level ( J:133634 )

• progeny of the founder mouse exhibit hyperinsulinemia

increased urine glucose level ( J:133634 )

• glucosuria was detected in the founder mouse at 19 weeks (score = 4), and in his progeny at 10 and 15 weeks

insulin resistance ( J:133634 )

• progeny of the index mouse exhibit insulin resistance

renal/urinary system

increased urine glucose level ( J:133634 )

• glucosuria was detected in the founder mouse at 19 weeks (score = 4), and in his progeny at 10 and 15 weeks

Genotype
MGI:3839918

cn4

• Allelic Composition: Sim1^{tm1.1(cre)Gld}/Sim1⁺; Tg(CAG-Bgeo,-AlstR,-EGFP)192Gld/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * SJL

nervous system

abnormal CNS synaptic transmission ( J:147245 )

• marked decrease in the rhythmicity of spinal cord locomotor like outputs and increase in the variance of flexor related bursts between the left and right halves in the presence of allatostatin

behavior/neurological

abnormal gait ( J:147245 )

• after application of allatostatin to the L2 - L4 segments 5 of 8 mice showed profound changes in their gate with changes in the timing and duration of both the stance and swing phases of the gait

• however, in the absence of treatment no gait abnormalities were seen

Genotype
MGI:3839917

cn5

• Allelic Composition: Gt(ROSA)26Sor^{tm2(GFP/tetX)Gld}/Gt(ROSA)26Sor⁺; Sim1^{tm1.1(cre)Gld}/Sim1⁺
• Genetic Background: involves: C57BL/6 * SJL

nervous system

abnormal CNS synaptic transmission ( J:147245 )

• electroneurogram recordings from ventral roots indicates a suppression of synaptic transmission disrupting locomotor rhythm

• outputs from spinal cords show increased variability in the duration of individual motor bursts and in the length of the step cycle period which may be coupled with asymmetry in the duration of flexor bursts between the right and left sides of the spinal cord

• spinal cords show impaired production of locomotor like oscillations following induction with NMDA and 5-hydroxytryptamine or after electrical stimulation of sensory afferents

Genotype
MGI:3613782

cx6

• Allelic Composition: Sim1^tm1Fan/Sim1⁺; Sim2^tm1Fan/Sim2^tm1Fan
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

abnormal nervous system tract morphology ( J:104419 )

• at E18.5, the principal mammillary axonal tract appears less prominent similar to mice homozygous for Sim1^tm1Fan alone

Genotype
MGI:3036853

cx7

• Allelic Composition: Sim1^tm1Fan/Sim1⁺; Sim2^tm1Fan/Sim2⁺
• Genetic Background: involves: 129/Sv * C57BL/6

growth/size/body

increased susceptibility to weight gain ( J:76787 )

• after 7 months the average weight was identical to that of mice heterozygous only for Sim1^tm1Fan

nervous system

abnormal diencephalon morphology ( J:76787 )

• paraventricular nucleus and supraoptic nuclei are hypocellular

• the phenotype is identical to that of mice heterozygous only for Sim1^tm1Fan

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:76787