Mouse Genome Informatics
hm1
    Adrb2tm1Bkk/Adrb2tm1Bkk
FVB.129-Adrb2tm1Bkk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue
• represent a smaller proportion of total body weight than wild-type fat pads

behavior/neurological
N
• daily locomotor activity is similar to wild-type during 48 hours of observation (J:55552)

cardiovascular system
• 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
• in response to isoproterenol treatement, the normal hypotensive response was blunted relative to rapid response in wild-type
• daily locomotor activity is similar to wild-type during 48 hours of observation

growth/size
• weight is significantly less than wild-type mice

homeostasis/metabolism
N
• no significant differences are seen in body density, free fatty acid levels, and serum glycerol relative to controls (J:55552)
• ratio is lower in mutants during exercise (greater oxygen consumption than wild-type)
• 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


Mouse Genome Informatics
hm2
    Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• decreased osteoclast surface in homozygous mutant bones
• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation
• bone resorption did not increase in gonadectomized homozygous mutant mice
• decrease in urinary elimination of deoxypyridinoline, a marker of osteoclast function
• 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
• increased bone formation rate and decreased bone resorption
• 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

hematopoietic system
• decreased osteoclast surface in homozygous mutant bones
• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation
• bone resorption did not increase in gonadectomized homozygous mutant mice
• decrease in urinary elimination of deoxypyridinoline, a marker of osteoclast function

immune system
• decreased osteoclast surface in homozygous mutant bones
• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation
• bone resorption did not increase in gonadectomized homozygous mutant mice
• decrease in urinary elimination of deoxypyridinoline, a marker of osteoclast function

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


Mouse Genome Informatics
hm3
    Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• increase in apoptosis in the ganglion cell layer
• decrease in retinal thickness at 2 months of age
• GFAP protein levels are increased in retinal Muller cells, indicating activated Muller cells
• increase in apoptosis in the ganglion cell layer
• decrease in cell number in the ganglion cell layer at 2 months of age
• oscillatory potential amplitudes are reduced at 2 months of age
• A-wave amplitudes are reduced at high light intensity
• B-wave amplitudes are reduced at 2 months of age

immune system
• increase in TNF-alpha in retinal lysates

nervous system
• GFAP protein levels are increased in retinal Muller cells, indicating activated Muller cells
• decrease in cell number in the ganglion cell layer at 2 months of age

cellular
• increase in apoptosis in the ganglion cell layer


Mouse Genome Informatics
ht4
    Adrb2tm1Bkk/Adrb2+
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• decreased number of tartrate-resistant acid phosphatase (TRAP)-positive multi-nucleated osteoclasts, indicating defective osteoclast differentiation
• increased bone volume/tissue volume and bone formation rate, showing a severe high bone mass phenotype at 6 months of age
• increased bone formation rate and decreased bone resorption

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

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

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


Mouse Genome Informatics
cx5
    Adrb1tm1Bkk/Adrb1tm1Bkk
Adrb2tm1Bkk/Adrb2tm1Bkk

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
N
• exhibit normal bone mass at 6 months of age (J:97566)


Mouse Genome Informatics
cx6
    Adrb1tm1Bkk/Adrb1tm1Bkk
Adrb2tm1Bkk/Adrb2tm1Bkk

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 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
• reduced cardiac contractility in awake and in anesthetized mice
• 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
• reduced O2 consumption during exercise and reduced CO2 production during exercise, but normal total exercise capacity
• abnormal responses to pharmacological stimuli; attenuation of the normal bradycardia and monophasic hypertension in response to epinephrine administration
• abnormal responses to pharmacological stimuli; attenuation of the normal tachycardia and hypotensive responses to isoproterenol administration

muscle
• reduced cardiac contractility in awake and in anesthetized mice


Mouse Genome Informatics
cx7
    Adrb1tm1Bkk/Adrb1tm1Bkk
Adrb2tm1Bkk/Adrb2tm1Bkk
Adrb3tm1Lowl/Adrb3tm1Lowl

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue
• obesity attributable to increased fat mass
• interscapular brown adipose tissue (BAT) enlarged and pale
• BAT contained large cells with unilocular triglyceride deposits

endocrine/exocrine glands
N
• normal thyroid hormone levels (J:79309)

growth/size
• obesity attributable to increased fat mass
• 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
• normal body temperature under conventional housing conditions, but exposure to cold (22oC) produced rapid decline in core body temperature
• failure of diet-induced thermogenesis
• increased leptin levels
• reduced metabolic rate, measured by O2 consumption
• isoproterenol exposure failed to increase O2 consumption

Mouse Models of Human Disease
OMIM IDRef(s)
Obesity 601665 J:79309