Phenotypes associated with this allele

• Allele Symbol: Adra1b^tm1Cta
• Allele Name: targeted mutation 1, Susanna Cotecchia
• Allele ID: MGI:2148638
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Adra1b^tm1Cta/Adra1b^tm1Cta	involves: 129 * C57BL/6J	MGI:4361022
hm2	Adra1b^tm1Cta/Adra1b^tm1Cta	involves: 129P2/OlaHsd	MGI:2677149
hm3	Adra1b^tm1Cta/Adra1b^tm1Cta	involves: 129P2/OlaHsd * C57BL/6J	MGI:3689189
cx4	Adra1a^tm1Pcs/Adra1a^tm1Pcs Adra1b^tm1Cta/Adra1b^tm1Cta	B6.129-Adra1b^tm1Cta Adra1a^tm1Pcs	MGI:3689510
cx5	Adra1a^tm1Pcs/Adra1a^tm1Pcs Adra1b^tm1Cta/Adra1b^tm1Cta	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N	MGI:3689509

Genotype
MGI:4361022

hm1

• Allelic Composition: Adra1b^tm1Cta/Adra1b^tm1Cta
• Genetic Background: involves: 129 * C57BL/6J

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

reproductive system

reproductive system phenotype ( J:125763 )

N • female homozygotes show no significant differences in follicular development, rate of pregnancy, or number of live pups/litter relative to wild-type controls

decreased male germ cell number ( J:125763 )

♂ • infertile males exhibit absence of round and elongated spermatids in seminiferous tubules

♂ • most early pachytene-like spermatocytes are apoptotic; the remaining spermatogenic cells observed are spermatogonia and rare preleptotene/leptotene spermatocytes

abnormal male germ cell apoptosis ( J:125763 )

♂ • in infertile males, a population of early meiotic cells exhibits apoptosis, as indicated by TUNEL analysis

small seminal vesicle ( J:125763 )

♂ • in infertile males, the size of seminal vesicles is significantly reduced

abnormal seminiferous tubule morphology ( J:125763 )

♂ • infertile males display Sertoli cell clusters in the tubule lumen due to unfolding of the seminiferous tubule wall

♂ • however, no extensive disruption of the seminiferous epithelium is observed in older hypofertile or infertile males

abnormal Sertoli cell morphology ( J:125763 )

♂ • infertile males display extensive vacuolization of Sertoli cells

small seminiferous tubules ( J:125763 )

♂ • in infertile males, the absolute volume of seminiferous tubules is decreased by 99% and the diameter of tubules is reduced to 50% of that in wild-type males

♂ • in hypofertile males, seminiferous tubule volume is less dramatically reduced, with no significant changes in overall histology or tubule diameter relative to wild-type males

small testis ( J:125763 )

♂ • in infertile males, testicular volume is reduced by 96%

♂ • in hypofertile males, testicular volume is less drastically reduced compared with infertile mice

decreased testis weight ( J:125763 )

♂ • in infertile males, testicular weight is reduced to 16% of that in wild-type males

♂ • in hypofertile males, testicular weight is reduced to 73% of that in wild-type males

decreased testes secretion ( J:125763 )

♂ • in vitro, whole testes from infertile males display a 40% decrease in testosterone release relative to hypofertile males; however, the mean absolute volume of Leydig cells per testis remains unchanged, suggesting impairment of the steroidogenic capacity of Leydig cells in infertile males

♂ • in vivo, adult infertile males exhibit a higher intratesticular content of inhibin B (19030 pg/testis) relative to hypofertile and wild-type males (9317 and 5314 pg/testis, respectively, values not significantly different)

arrest of spermatogenesis ( J:125763 )

♂ • in infertile males, spermatogenesis is arrested prior to early spermiogenic stages as indicated by the absence of round and elongated spermatids in seminiferous tubules

♂ • in contrast, no apparent disruption of spermatogenesis is noted in hypofertile males

decreased litter size ( J:125763 )

• litters sired by hypofertile males are reduced (6.00.4 vs 8.50.3 pups/litter in wild-type males)

male infertility ( J:125763 )

♂ • 27% of adult male homozygotes (3-8 months) are infertile

reduced male fertility ( J:125763 )

♂ • the remaining 73% of adult male homozygotes (3-8 months) are hypofertile, yielding fewer copulatory plugs and smaller litter sizes than wild-type males

endocrine/exocrine glands

small seminal vesicle ( J:125763 )

♂ • in infertile males, the size of seminal vesicles is significantly reduced

abnormal seminiferous tubule morphology ( J:125763 )

♂ • infertile males display Sertoli cell clusters in the tubule lumen due to unfolding of the seminiferous tubule wall

♂ • however, no extensive disruption of the seminiferous epithelium is observed in older hypofertile or infertile males

abnormal Sertoli cell morphology ( J:125763 )

♂ • infertile males display extensive vacuolization of Sertoli cells

small seminiferous tubules ( J:125763 )

♂ • in infertile males, the absolute volume of seminiferous tubules is decreased by 99% and the diameter of tubules is reduced to 50% of that in wild-type males

♂ • in hypofertile males, seminiferous tubule volume is less dramatically reduced, with no significant changes in overall histology or tubule diameter relative to wild-type males

small testis ( J:125763 )

♂ • in infertile males, testicular volume is reduced by 96%

♂ • in hypofertile males, testicular volume is less drastically reduced compared with infertile mice

decreased testis weight ( J:125763 )

♂ • in infertile males, testicular weight is reduced to 16% of that in wild-type males

♂ • in hypofertile males, testicular weight is reduced to 73% of that in wild-type males

decreased testes secretion ( J:125763 )

♂ • in vitro, whole testes from infertile males display a 40% decrease in testosterone release relative to hypofertile males; however, the mean absolute volume of Leydig cells per testis remains unchanged, suggesting impairment of the steroidogenic capacity of Leydig cells in infertile males

♂ • in vivo, adult infertile males exhibit a higher intratesticular content of inhibin B (19030 pg/testis) relative to hypofertile and wild-type males (9317 and 5314 pg/testis, respectively, values not significantly different)

homeostasis/metabolism

decreased circulating testosterone level ( J:125763 )

• at 4 months of age, infertile males show a 81% decrease in basal levels of plasma testosterone relative to wild-type controls

• hypofertile males display a 55% decrease in basal levels of plasma testosterone relative to wild-type controls

increased circulating luteinizing hormone level ( J:125763 )

• at 4 months of age, infertile males display significantly higher LH plasma levels than hypofertile and wild-type males; no significant differences are noted between the latter groups of males

• in contrast, basal plasma FSH concentrations remain normal in both infertile and hypofertile males

cellular

decreased male germ cell number ( J:125763 )

♂ • infertile males exhibit absence of round and elongated spermatids in seminiferous tubules

♂ • most early pachytene-like spermatocytes are apoptotic; the remaining spermatogenic cells observed are spermatogonia and rare preleptotene/leptotene spermatocytes

abnormal male germ cell apoptosis ( J:125763 )

♂ • in infertile males, a population of early meiotic cells exhibits apoptosis, as indicated by TUNEL analysis

Genotype
MGI:2677149

hm2

• Allelic Composition: Adra1b^tm1Cta/Adra1b^tm1Cta
• Genetic Background: involves: 129P2/OlaHsd

cardiovascular system

abnormal heart left ventricle morphology ( J:103581 )

• left ventricular volume is higher

decreased cardiac muscle contractility ( J:43591 , J:103581 )

• phenylephrine-induced contractions of aortic rings are decreased by 25% (J:43591)

• baseline myocardial contractility is lower, as reflected by dP/dt (J:103581)

• transient bilateral carotid occlusion results in a minimal increase in myocardial contractility instead of the enhanced contractility seen in wild-type (J:103581)

decreased heart rate ( J:103581 )

• transient bilateral carotid occlusion results in a decrease in heart rate compared to a slight increase in treated wild-type, however baseline heart rate is normal

abnormal systemic arterial blood pressure ( J:43591 )

• mean arterial blood pressure response to phenylephrine is decreased by 45%

• mean arterial blood pressure response to norepinephrine is also decreased although to a lesser extent than seen with phenylephrine

decreased systemic arterial blood pressure ( J:103581 )

• exhibit impaired pressor response to a hypotensive stimulus, with marked attenuation in the change in systolic blood pressure and in the percent change in the end-systolic pressure-volume relationship after transient bilateral carotid occlusion

decreased systemic arterial systolic blood pressure ( J:103581 )

• baseline systolic blood pressure and Ea are lower

decreased vasoconstriction ( J:103581 )

• exhibit a reduction in mesenteric vascular responses to endogenous norepinephrine compared to wild-type, indicating reduced vasoconstriction in response to norepinephrine

muscle

decreased cardiac muscle contractility ( J:43591 , J:103581 )

• phenylephrine-induced contractions of aortic rings are decreased by 25% (J:43591)

• baseline myocardial contractility is lower, as reflected by dP/dt (J:103581)

• transient bilateral carotid occlusion results in a minimal increase in myocardial contractility instead of the enhanced contractility seen in wild-type (J:103581)

decreased vasoconstriction ( J:103581 )

• exhibit a reduction in mesenteric vascular responses to endogenous norepinephrine compared to wild-type, indicating reduced vasoconstriction in response to norepinephrine

behavior/neurological

impaired passive avoidance behavior ( J:102553 )

• 4-5 month old homozygotes show impaired retention of an inhibitory avoidance task after receiving a stressful electric stimuli

decreased exploration in new environment ( J:102553 )

• 4-5 month old homozygotes show significantly reduced horizontal exploratory activity and a reduced rearing behavior (vertical activity) in the open field

nervous system

abnormal baroreceptor physiology ( J:103581 )

• transient bilateral carotid occlusion to test cardiovascular responses to a hypotensive stimuli produced an attenuated pressor response, indicating an abnormal baroreflex activity

Genotype
MGI:3689189

hm3

• Allelic Composition: Adra1b^tm1Cta/Adra1b^tm1Cta
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

behavior/neurological

impaired behavioral response to addictive substance ( J:76004 )

• locomotor hyperactivities induced by D-amphetamine, cocaine, or morphine are dramatically decreased compared to wild-type, however exhibit normal locomotor responses to novelty, saline injection, scopolamine, and chloro-APB

• behavioral sensitizations induced by repeated administration of D-amphetamine, cocaine, or morphine are decreased

abnormal learning/memory/conditioning ( J:68177 )

impaired conditioned place preference behavior ( J:76004 )

• rewarding properties of cocaine and morphine are not observed in the conditioned place preference paradigm

increased exploration in new environment ( J:68177 )

• show enhanced reactivity to new situations; they are faster to enter the new environment and cover longer paths in the open field

• on the homing board, behave similarly to controls during the training phase, except for the first session during which the homozygotes were faster to reach the correct hole, indicating enhanced exploratory behavior

abnormal spatial learning ( J:68177 )

• in the hidden platform water maze, mutants show no bias toward the position of the escape hidden platform, although they can swim normally to a visible platform, indicating that the absence of proximal cues impairs performance

abnormal response to novel object ( J:68177 )

• show enhanced reactivity to new situations; spend more time exploring new objects, however show a strong habituation rate as they are not more active than controls after 3 trials in the object novelty test

muscle

decreased skeletal muscle glycogen level ( J:87718 )

• muscle glycogen content is reduced in both fed and fasted mutants

liver/biliary system

increased liver glycogen level ( J:87718 )

• liver glycogen stores are 2-fold higher in the fed state compared with control but are mobilized at the same rate during the fed to fast transition or following glucagons injections

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:87718 )

• high fat diet for one month increases body weight in homozygotes but not controls

increased circulating leptin level ( J:87718 )

• show elevated leptin concentrations in the fed state and remain elevated at all times during the transition to fasting

decreased circulating free fatty acids level ( J:87718 )

• free fatty acid levels are lower after 6 hours of fasting, however are normal in the fed state

abnormal glucose homeostasis ( J:87718 )

• glucose turnover rate in the basal state is reduced by 20%

hyperglycemia ( J:87718 )

• blood glucose levels remain significantly higher during the first 6 hours of fasting, however the return to control levels after 24 hours and are normal in the fed state

increased circulating insulin level ( J:87718 )

• plasma insulin levels during the transition to fasting remain markedly elevated and return to control levels after 24 hours, however fed state levels are normal

impaired glucose tolerance ( J:87718 )

• high fat diet for one month increases glucose intolerance in homozygotes but not controls

increased liver glycogen level ( J:87718 )

• liver glycogen stores are 2-fold higher in the fed state compared with control but are mobilized at the same rate during the fed to fast transition or following glucagons injections

decreased skeletal muscle glycogen level ( J:87718 )

• muscle glycogen content is reduced in both fed and fasted mutants

insulin resistance ( J:87718 )

• insulin-increased glucose turnover is 20 and 15% lower at low and high insulin infusion rates, respectively

adipose tissue

increased percent body fat/body weight ( J:87718 )

• total body fat is increased by about 60% even though body weight is normal

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:87718 )

• hyperinsulinemia in the post-absorptive phase is normalized by atropine or methyl-atropine indicating elevated parasympathetic activity in pancreatic beta cells

growth/size/body

increased susceptibility to diet-induced obesity ( J:87718 )

• high fat diet for one month increases body weight in homozygotes but not controls

Genotype
MGI:3689510

cx4

• Allelic Composition: Adra1a^tm1Pcs/Adra1a^tm1Pcs; Adra1b^tm1Cta/Adra1b^tm1Cta
• Genetic Background: B6.129-Adra1b^tm1Cta Adra1a^tm1Pcs

cardiovascular system

decreased myocardial fiber size ( J:83876 )

• myocyte cross-sectional area and surface area are 25% smaller in males than in wild-type

small heart ( J:83876 )

• hearts are smaller in males, but not females, due to smaller myocytes

muscle

decreased myocardial fiber size ( J:83876 )

• myocyte cross-sectional area and surface area are 25% smaller in males than in wild-type

Genotype
MGI:3689509

cx5

• Allelic Composition: Adra1a^tm1Pcs/Adra1a^tm1Pcs; Adra1b^tm1Cta/Adra1b^tm1Cta
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:83876 )

♂ • males show increased mortality after pressure overload (transverse aortic constriction), with only 56% surviving 14 days post TAC

cardiovascular system

decreased myocardial fiber size ( J:83876 )

♂ • myocyte cross-sectional area is reduced by 33% in male hearts

abnormal heart size ( J:83876 )

small heart ( J:83876 )

♂ • hearts are smaller in males, but not females, due to smaller myocytes

decreased heart weight ( J:83876 )

♂ • male atrial, ventricular, and total heart wet weights are reduced by 18%, 16%, and 16%, respectively, however females have normal sized hearts

♂ • male heart growth after weaning is 40% less than in wild-type

abnormal cardiovascular system physiology ( J:83876 )

decreased cardiac output ( J:83876 )

♂ • cardiac output is reduced by 27% in conscious males

decreased cardiac stroke volume ( J:83876 )

♂ • conscious males show a 20% reduction in end-diastolic volume which causes a smaller stroke volume

abnormal cardiac muscle contractility ( J:102648 )

• ventricular trabeculae have higher submaximal force at 2 mM extracellular calcium concentration than wild-type, however peaks of fura-2 calcium transients are not different, suggesting the myocardium has increased myofilament calcium sensitivity

• ventricular trabeculae have lower maximal force than wild-type at high extracellular calcium concentrations (6 mM), however peak cystolic calcium concentration is not different

• maximum tetanic force of trabeculae is lower than in wild-type

• trabeculae develop higher forces at all pacing rates tested than wild-type

increased heart left ventricle muscle contractility ( J:83876 )

♂ • in anesthetized males, but not conscious males, indices of contractility (fractional shortening and ejection fraction) are increased slightly and left ventricular wall thickness and mass and end-systolic chamber size are reduced and the left ventricle end-diastolic chamber size tends to be smaller

increased left ventricle developed pressure ( J:102648 )

• 2.5 mM calcium Langendorff-perfused hearts have higher developed pressure than wild-type

decreased heart rate ( J:83876 )

• conscious young males and females show reduced heart rate, although blood pressure is normal and anesthetized mice show no difference in heart rate

abnormal myocardial fiber physiology ( J:102648 )

• myocardium shows increased myofilament calcium-sensitivity and decreased responsiveness to beta-adrenergic stimulation

increased response of heart to induced stress ( J:83876 )

• males show increased mortality and heart failure after pressure overload

congestive heart failure ( J:83876 )

♂ • heart failure is seen in males exposed to pressure overload

homeostasis/metabolism

impaired exercise endurance ( J:83876 )

♂ • males run significantly less in both a voluntary and forced exercise test, indicating reduced exercise capacity

increased response of heart to induced stress ( J:83876 )

• males show increased mortality and heart failure after pressure overload

muscle

decreased myocardial fiber size ( J:83876 )

♂ • myocyte cross-sectional area is reduced by 33% in male hearts

abnormal cardiac muscle contractility ( J:102648 )

• ventricular trabeculae have higher submaximal force at 2 mM extracellular calcium concentration than wild-type, however peaks of fura-2 calcium transients are not different, suggesting the myocardium has increased myofilament calcium sensitivity

• ventricular trabeculae have lower maximal force than wild-type at high extracellular calcium concentrations (6 mM), however peak cystolic calcium concentration is not different

• maximum tetanic force of trabeculae is lower than in wild-type

• trabeculae develop higher forces at all pacing rates tested than wild-type

increased heart left ventricle muscle contractility ( J:83876 )

♂ • in anesthetized males, but not conscious males, indices of contractility (fractional shortening and ejection fraction) are increased slightly and left ventricular wall thickness and mass and end-systolic chamber size are reduced and the left ventricle end-diastolic chamber size tends to be smaller

renal/urinary system

enlarged kidney ( J:83876 )

♀ • females exhibit larger kidneys than wild-type

behavior/neurological

impaired exercise endurance ( J:83876 )

♂ • males run significantly less in both a voluntary and forced exercise test, indicating reduced exercise capacity

growth/size/body

enlarged kidney ( J:83876 )

♀ • females exhibit larger kidneys than wild-type