Phenotypes associated with this allele

• Allele Symbol: Adrb2^tm1Bkk
• Allele Name: targeted mutation 1, Brian K Kobilka
• Allele ID: MGI:1859675
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Adrb2^tm1Bkk/Adrb2^tm1Bkk	FVB.129-Adrb2^tm1Bkk	MGI:3710655
hm2	Adrb2^tm1Bkk/Adrb2^tm1Bkk	involves: 129S1/Sv * 129X1/SvJ	MGI:3579020
hm3	Adrb2^tm1Bkk/Adrb2^tm1Bkk	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N	MGI:5565473
ht4	Adrb2^tm1Bkk/Adrb2^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3579023
cx5	Adrb1^tm1Bkk/Adrb1^tm1Bkk Adrb2^tm1Bkk/Adrb2^tm1Bkk	involves: 129S1/Sv * 129X1/SvJ	MGI:3579029
cx6	Adrb1^tm1Bkk/Adrb1^tm1Bkk Adrb2^tm1Bkk/Adrb2^tm1Bkk	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N	MGI:2388098
cx7	Adrb1^tm1Bkk/Adrb1^tm1Bkk Adrb2^tm1Bkk/Adrb2^tm1Bkk Adrb3^tm1Lowl/Adrb3^tm1Lowl	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N	MGI:2388265

Genotype
MGI:3710655

hm1

• Allelic Composition: Adrb2^tm1Bkk/Adrb2^tm1Bkk
• Genetic Background: FVB.129-Adrb2^tm1Bkk

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

adipose tissue

abnormal epididymal fat pad morphology ( J:55552 )

• represent a smaller proportion of total body weight than wild-type fat pads

behavior/neurological

behavior/neurological phenotype ( J:55552 )

N • daily locomotor activity is similar to wild-type during 48 hours of observation

cardiovascular system

abnormal heart rate ( J:55552 )

• mutants show trend to increased heart rate with epinephrine, whereas wild-type show a trend to decreased rate, but difference is not significant

• isoproterenol treatment induced tachycardia in mutants and wild-type similarly

decreased mean systemic arterial blood pressure ( J:55552 )

• in response to isoproterenol treatement, the normal hypotensive response was blunted relative to rapid response in wild-type

increased systemic arterial blood pressure ( J:55552 )

• daily locomotor activity is similar to wild-type during 48 hours of observation

growth/size/body

decreased body weight ( J:55552 )

• weight is significantly less than wild-type mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:55552 )

N • no significant differences are seen in body density, free fatty acid levels, and serum glycerol relative to controls

decreased respiratory quotient ( J:55552 )

• ratio is lower in mutants during exercise (greater oxygen consumption than wild-type)

enhanced exercise endurance ( J:55552 )

• on a graded treadmill, null mice show longer period of exercise compared to wild-type; null mice cover 582 meters vs 471 meters for wild-type

Genotype
MGI:3579020

hm2

• Allelic Composition: Adrb2^tm1Bkk/Adrb2^tm1Bkk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

skeleton

abnormal osteoblast physiology ( J:97566 )

• isoproterenol did not enhance the generation of osteoclasts when homozygous mutant osteoblasts were co-cultured with wildtype bone marrow macrophages, like it did in wildtype

abnormal osteoclast morphology ( J:97566 )

• decreased osteoclast surface in homozygous mutant bones

abnormal osteoclast differentiation ( J:97566 )

• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation

abnormal osteoclast physiology ( J:97566 )

• bone resorption did not increase in gonadectomized homozygous mutant mice

• decrease in urinary elimination of deoxypyridinoline, a marker of osteoclast function

increased bone mass ( J:97566 )

• increased bone volume/tissue volume and bone formation rate, showing a severe high bone mass phenotype at 6 months of age

• long-term leptin intracerebroventricular infusion or gonadectomy did not reduce bone mass of homozygous mutant mice

abnormal bone resorption ( J:97566 )

• increased bone formation rate and decreased bone resorption

decreased bone resorption ( J:97566 )

hematopoietic system

abnormal osteoclast morphology ( J:97566 )

• decreased osteoclast surface in homozygous mutant bones

abnormal osteoclast differentiation ( J:97566 )

• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation

abnormal osteoclast physiology ( J:97566 )

• bone resorption did not increase in gonadectomized homozygous mutant mice

• decrease in urinary elimination of deoxypyridinoline, a marker of osteoclast function

immune system

abnormal osteoclast morphology ( J:97566 )

• decreased osteoclast surface in homozygous mutant bones

abnormal osteoclast differentiation ( J:97566 )

• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation

abnormal osteoclast physiology ( J:97566 )

• bone resorption did not increase in gonadectomized homozygous mutant mice

• decrease in urinary elimination of deoxypyridinoline, a marker of osteoclast function

cellular

abnormal osteoclast differentiation ( J:97566 )

• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation

abnormal osteoblast physiology ( J:97566 )

• isoproterenol did not enhance the generation of osteoclasts when homozygous mutant osteoblasts were co-cultured with wildtype bone marrow macrophages, like it did in wildtype

Genotype
MGI:5565473

hm3

• Allelic Composition: Adrb2^tm1Bkk/Adrb2^tm1Bkk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N

vision/eye

increased retina apoptosis ( J:204379 )

• increase in apoptosis in the ganglion cell layer

abnormal retina morphology ( J:204379 )

• decrease in retinal thickness at 2 months of age

abnormal Muller cell morphology ( J:204379 )

• GFAP protein levels are increased in retinal Muller cells, indicating activated Muller cells

abnormal retina ganglion layer morphology ( J:204379 )

• increase in apoptosis in the ganglion cell layer

decreased retina ganglion cell number ( J:204379 )

• decrease in cell number in the ganglion cell layer at 2 months of age

abnormal electroretinogram waveform feature ( J:204379 )

• oscillatory potential amplitudes are reduced at 2 months of age

decreased a-wave amplitude ( J:204379 )

• A-wave amplitudes are reduced at high light intensity

decreased b-wave amplitude ( J:204379 )

• B-wave amplitudes are reduced at 2 months of age

immune system

increased tumor necrosis factor secretion ( J:204379 )

• increase in TNF-alpha in retinal lysates

nervous system

abnormal Muller cell morphology ( J:204379 )

• GFAP protein levels are increased in retinal Muller cells, indicating activated Muller cells

decreased retina ganglion cell number ( J:204379 )

• decrease in cell number in the ganglion cell layer at 2 months of age

cellular

increased retina apoptosis ( J:204379 )

• increase in apoptosis in the ganglion cell layer

Genotype
MGI:3579023

ht4

• Allelic Composition: Adrb2^tm1Bkk/Adrb2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

skeleton

abnormal osteoclast differentiation ( J:97566 )

• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation

increased bone volume ( J:97566 )

• increased bone volume/tissue volume and bone formation rate, showing a severe high bone mass phenotype at 6 months of age

abnormal bone resorption ( J:97566 )

• increased bone formation rate and decreased bone resorption

decreased bone resorption ( J:97566 )

hematopoietic system

abnormal osteoclast differentiation ( J:97566 )

• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation

immune system

abnormal osteoclast differentiation ( J:97566 )

• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation

cellular

abnormal osteoclast differentiation ( J:97566 )

• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation

Genotype
MGI:3579029

cx5

• Allelic Composition: Adrb1^tm1Bkk/Adrb1^tm1Bkk; Adrb2^tm1Bkk/Adrb2^tm1Bkk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

skeleton

skeleton phenotype ( J:97566 )

N • exhibit normal bone mass at 6 months of age

Genotype
MGI:2388098

cx6

• Allelic Composition: Adrb1^tm1Bkk/Adrb1^tm1Bkk; Adrb2^tm1Bkk/Adrb2^tm1Bkk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N

cardiovascular system

abnormal cardiovascular system physiology ( J:55553 )

• abnormal responses to pharmacological stimuli; attenuation of both the normal tachycardia and hypotensive responses to isoproterenol administration and bradycardia and monophasic hypertension in response to epinephrine administration

decreased cardiac muscle contractility ( J:55553 )

• reduced cardiac contractility in awake and in anesthetized mice

decreased heart rate ( J:55553 )

• decreased heart rate in response to exercise, but normal basal heart rate, normal basal mean arterial blood pressure and normal blood pressure changes in response to exercise

homeostasis/metabolism

decreased oxygen consumption ( J:55553 )

• reduced O₂ consumption during exercise and reduced CO₂ production during exercise, but normal total exercise capacity

abnormal response/metabolism to endogenous compounds ( J:55553 )

• abnormal responses to pharmacological stimuli; attenuation of the normal bradycardia and monophasic hypertension in response to epinephrine administration

abnormal physiological response to xenobiotic ( J:55553 )

• abnormal responses to pharmacological stimuli; attenuation of the normal tachycardia and hypotensive responses to isoproterenol administration

muscle

decreased cardiac muscle contractility ( J:55553 )

• reduced cardiac contractility in awake and in anesthetized mice

Genotype
MGI:2388265

cx7

• Allelic Composition: Adrb1^tm1Bkk/Adrb1^tm1Bkk; Adrb2^tm1Bkk/Adrb2^tm1Bkk; Adrb3^tm1Lowl/Adrb3^tm1Lowl
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N

adipose tissue

increased total body fat amount ( J:79309 )

• obesity attributable to increased fat mass

abnormal brown adipose tissue morphology ( J:79309 )

• interscapular brown adipose tissue (BAT) enlarged and pale

• BAT contained large cells with unilocular triglyceride deposits

increased brown fat cell size ( J:79309 )

increased interscapular fat pad weight ( J:79309 )

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:79309 )

N • normal thyroid hormone levels

growth/size/body

increased body weight ( J:79309 )

obese ( J:79309 )

• on regular Chow diet, mildly obese by 20 weeks; increased obesity on high fat diet (58% of kcal from fat)

• normal food intake and normal physical activity on both normal and high fat diets were observed, however

homeostasis/metabolism

impaired adaptive thermogenesis ( J:79309 )

• normal body temperature under conventional housing conditions, but exposure to cold (22^oC) produced rapid decline in core body temperature

• failure of diet-induced thermogenesis

increased circulating leptin level ( J:79309 )

• increased leptin levels

decreased oxygen consumption ( J:79309 )

• reduced metabolic rate, measured by O₂ consumption

• isoproterenol exposure failed to increase O₂ consumption

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:79309