Phenotypes associated with this allele

• Allele Symbol: Drd2^tm1Ebo
• Allele Name: targeted mutation 1, Emiliana Borrelli
• Allele ID: MGI:2387895
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Drd2^tm1Ebo/Drd2^tm1Ebo	B6.129S2-Drd2^tm1Ebo	MGI:4441281
hm2	Drd2^tm1Ebo/Drd2^tm1Ebo	involves: 129S2/SvPas * C57BL/6	MGI:2675764
ht3	Drd2^tm1Ebo/Drd2^+	involves: 129S2/SvPas * C57BL/6	MGI:3615305
cx4	Drd2^tm1Ebo/Drd2^tm1Ebo Drd3^tm1Dac/Drd3^tm1Dac	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6	MGI:4839981
cx5	Drd1^tm1Jcd/Drd1^tm1Jcd Drd2^tm1Ebo/Drd2^+	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6	MGI:4440953
cx6	Drd1^tm1Jcd/Drd1^tm1Jcd Drd2^tm1Ebo/Drd2^tm1Ebo	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6	MGI:4440949
cx7	Drd1^tm1Jcd/Drd1^+ Drd2^tm1Ebo/Drd2^tm1Ebo	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6	MGI:4441067

Genotype
MGI:4441281

hm1

• Allelic Composition: Drd2^tm1Ebo/Drd2^tm1Ebo
• Genetic Background: B6.129S2-Drd2^tm1Ebo

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

nervous system

increased susceptibility to neuronal excitotoxicity ( J:65767 )

• at 5 days after kainic acid treatment (20 or 35 mg/kg), homozygotes exhibit extensive hippocampal cell loss and tissue sclerosis in the CA3 region, whereas wild-type controls show no hippocampal cell damage

homeostasis/metabolism

increased susceptibility to neuronal excitotoxicity ( J:65767 )

• at 5 days after kainic acid treatment (20 or 35 mg/kg), homozygotes exhibit extensive hippocampal cell loss and tissue sclerosis in the CA3 region, whereas wild-type controls show no hippocampal cell damage

cellular

increased susceptibility to neuronal excitotoxicity ( J:65767 )

• at 5 days after kainic acid treatment (20 or 35 mg/kg), homozygotes exhibit extensive hippocampal cell loss and tissue sclerosis in the CA3 region, whereas wild-type controls show no hippocampal cell damage

Genotype
MGI:2675764

hm2

• Allelic Composition: Drd2^tm1Ebo/Drd2^tm1Ebo
• Genetic Background: involves: 129S2/SvPas * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:111282 )

N • homozygotes exhibit a normal exploratory response in a stressful (highly illuminated) open field with unknown objects relative to wild-type controls

N • in response to morphine administration (2 and 6 mg/kg body weight), homozygous mutant and wild-type mice show a similar increase in horizontal locomotor activity under non-stressful conditions

N • in response to endogenous opioid administration (RB 101, 100 mg/kg body weight), homozygous mutant and wild-type mice show a similar increase in horizontal locomotor activity relative to saline-treated controls, indicating normal opioid-induced hyperlocomotion

N • following chronic administration of increasing doses of morphine , homozygotes show no differences in the incidence of naloxone-precipitated somatic signs of morphine withdrawal relative to similarly treated wild-type controls

abnormal behavior ( J:96229 )

• in a non-selective attention test, mice exhibit higher scanning times (measured by duration of individual rearing episodes) during the second part of the test compared with wild-type mice

increased susceptibility to pharmacologically induced seizures ( J:65767 )

• at 10 mg/kg kainic acid (i.p.), homozygotes display preconvulsive behaviors (rigid posture, tail stiffening, and forelimb extension) whereas wild-type and heterozygotes remain immobile

• at 20 mg/kg kainic acid, homozygotes exhibit obvious symptoms of limbic epileptic activity (repeated episodes of rearing with forelimb clonus, alternating with rigid posture and head bobbing), whereas wild-type and heterozygous controls display only preconvulsive signs

• however, at 35 mg/kg kainic acid, homozygotes exhibit repeated limbic seizures of the same severity as those observed in wild-type and heterozygous controls

impaired conditioned place preference behavior ( J:111282 )

• in response to s.c. morphine administration (3 mg/kg body weight), homozygotes, unlike wild-type controls, fail to display a significant increase in the time spent in the morphine-associated compartment during the testing phase of a conditioned place preference paradigm, indicating that opioid rewarding properties are suppressed

• in response to a higher morphine dose (9 mg/kg body weight), drug-naive homozygotes also fail to show place preference in the same place-conditioning paradigm, indicating lack of a developed tolerance to endogenous opioids

• however, morphine-treated homozygotes display a behavior similar to that of wild-type controls during the preconditioning phase of the place-conditioning paradigm, and retain a normal exploratory activity and locomotor response to morphine treatment

• homozygotes show a normal conditioned place preference when palatable food is used as reward, indicating that the motivational deficit affects morphine rewarding properties but not natural rewards

decreased fluid intake ( J:29045 )

• homozygotes display a 10-15% reduction in water intake relative to wild-type mice

decreased food intake ( J:29045 )

• homozygotes display a 10-15% reduction in food intake relative to wild-type mice

impaired coordination ( J:29045 )

• homozygotes spend significantly less time on the rotarod than heterozygous or wild-type mice

limp posture ( J:29045 )

• homozygotes display an abnormal posture, with fore- and hindpaws flattened to the ground

akinesia ( J:29045 )

abnormal gait ( J:29045 )

• when allowed to walk on a flat surface, homozygotes display an abnormal gait, with sprawled hind legs

decreased vertical activity ( J:29045 , J:96229 )

• homozygotes exhibit no vertical activity (rearing) in the open-field test (J:29045)

decreased locomotor activity ( J:29045 , J:96229 )

• homozygotes show a significant reduction in locomotion (74%) and backward movements in the open-field test (J:29045)

bradykinesia ( J:29045 )

• homozygotes show normal reflexes but exhibit slower movements relative to wild-type littermates

catalepsy ( J:29045 )

• homozygotes display a cataleptic-like behavior as quantified in the ring test

endocrine/exocrine glands

abnormal adrenal gland zona fasciculata morphology ( J:110599 )

• unlike in wild-type mice, the mutant zonae fasciculata and reticularis are fused in mutant mice

abnormal adrenal gland zona reticularis morphology ( J:110599 )

• unlike in wild-type mice, the mutant zonae fasciculata and reticularis are fused in mutant mice

enlarged adrenocortical cells ( J:110599 )

• at 4 months of age, homozygotes exhibit significant adrenocortical hypertrophy with the characteristic fusion of the zona fasciculata and reticularis seen in patients with Cushing's syndrome

adrenal cortical hyperplasia ( J:110599 )

• at 4 months of age, homozygotes exhibit significant adrenocortical hyperplasia relative to wild-type controls

decreased lactotroph cell size ( J:41857 )

• at 4 months of age, prolactin-positive cells appear smaller and more compact than normal

increased lactotroph cell number ( J:41857 )

• at 4 months of age, female homozygotes show an increased number of lactotrophs relative to wild-type controls

• aberrant proliferation of lactotrophs gives rise to tumors in aged mice

decreased somatotroph cell number ( J:41857 )

• at 4 months of age, female homozygotes show a 25% decrease in the number of GH-expressing cellls relative to wild-type controls

increased thyrotroph cell number ( J:41857 )

• at 4 months of age, female homozygotes show a 2-fold increase in thyrotroph cell number relative to wild-type controls

• however, plasma beta-TSH levels are not significantly increased

adenohypophysis hyperplasia ( J:41857 )

♀ • at 4 months of age, the anterior lobe of female mutant pituitaries shows an increase in both cell number and density relative to that in wild-type controls

enlarged pituitary gland ( J:41857 )

• at 4 months of age, homozygotes of both sexes display an enlarged pituitary

• however, pituitary enlargement is less pronounced in males

pituitary gland hyperplasia ( J:41857 )

• mutant pituitaries show absence of dopaminergic control (sites) resulting in pituitary cell proliferation

• male homozygotes display less prominent pituitary gland hyperplasia than age-matched female homozygotes

• hyperplasia appears to correlate with a progressive induction of prolactin receptor levels in the pituitary gland as homozygotes become older

• whereas hyperplasia of the intermediate lobe occurs earlier (7-8 weeks of age) and remains contained even in aged animals, hyperplasia of the anterior lobe is delayed (3-4 months) but progressive leading to tumors in aged mice

abnormal melanotroph morphology ( J:110599 )

• at 4 months of age, homozygotes display both increased melanotroph proliferation and altered cellular identity

pituitary intermediate lobe hyperplasia ( J:41857 , J:110599 )

• at 4 months of age, intermediate lobe hyperplasia is due to increased proliferation of POMC-producing melanotrophs (J:110599)

♀ • at 4 months of age, the intermediate lobe of female mutant pituitaries shows a 40% increase in cell number, but not in cell density, relative to that in wild-type controls (J:41857)

small ovary ( J:29045 )

♀

small testis ( J:29045 )

♂

increased pituitary adenoma incidence ( J:41857 )

• at 8-14 months of age, all female homozygotes display anterior pituitary tumors with nodular areas and large blood vessel infiltration

• male homozygotes develop anterior pituitary tumors much later than female homozygotes (19 months versus 8 months of age, respectively)

hypersecretion of corticosterone ( J:110599 )

• at 4 months of age, homozygotes display adrenal hypersecretion of corticosterone due to excess circulating ACTH levels

abnormal pituitary gland physiology ( J:110599 )

• at 4 months of age, homozygotes show a 2-fold increase in POMC expression that is specifically restricted to pituitary melanotrophs

• mutant melanotrophs lose their cell identity and display aberrant production of ACTH leading to adrenal hyperplasia

• however, expression of the hypothalamic corticotropin releasing hormone (CRF) involved in the regulation of POMC synthesis remains unaffected

growth/size/body

decreased body weight ( J:29045 )

• homozygotes exhibit a 15% reduction in body weight relative to wild-type mice

homeostasis/metabolism

increased susceptibility to neuronal excitotoxicity ( J:65767 )

• at 16 hrs after 20 or 35 mg/kg kainic acid administration, homozygotes, but not wild-type controls, display induction of Jun mRNA and the proapoptotic factor BAX, as well as fragmented DNA in CA3 cells and an increased number of TUNEL-positive cells, suggesting hippocampal cell death by apoptosis

• the extension of BAX labeling and tissue damage in the CA3 subfield are larger than that of TUNEL staining, indicating progressive apoptotic hippocampal cell death after kainic acid-induced seizures

• cell loss is detected only in the CA3 subfield but not in other regions of the hippocampus

• an extensive gliosis is observed in the CA3 subfield by GFAP immunohistochemistry

• the extent of CA3 cell damage following treatment with 35 mg/kg kainic acid is greater than that observed with 20 mg/kg, indicating a dose-dependent toxic effect; a higher number of TUNEL-positive cells and a larger extension of reactive gliosis are additionally observed in homozygotes treated with 35 mg/kg

• at 12 hrs after 35 mg/kg kainic acid administration, homozygotes show a stronger Jun induction in the hippocampus and cerebral cortex than wild-type controls, correlating with the occurrence of hippocampal cell death

decreased circulating estrogen level ( J:41857 )

• female homozygotes show a 70% reduction in serum estrogen levels relative to wild-type females

• male homozygotes display a 20% reduction in serum estrogen levels relative to wild-type males

• interestingly, female and male homozygotes display very similar serum estrogen levels (8 ng/l and 9 ng/ml, respectively)

increased circulating corticosterone level ( J:110599 )

• at 4 months of age, homozygotes show a 1.5-fold increase in plasma corticosterone levels relative to wild-type controls

decreased circulating growth hormone level ( J:41857 )

• at 4 months of age, plasma GH levels are reduced by 25% and 35% in male and female homozygotes, respectively

increased circulating pituitary hormone level ( J:110599 )

• at 4 months of age, homozygotes show a 5.7- and 2.7-fold increase in serum levels of beta-endorphin and alpha-MSH, respectively, relative to wild-type controls

increased circulating prolactin level ( J:41857 )

• in the absence of dopaminergic control, adult homozygotes show 10.9- and 5.3-fold higher serum prolactin levels in females and males, respectively, relative to wild-type controls

• female homozygotes show a 6-fold rise in plasma prolactin levels relative to male homozygotes (264 +/- 35.2 ng/ml versus 41.1 +/- 7.2 ng/ml, respectively), whereas wild-type females show only a 3-fold difference in prolactin levels relative to wild-type males

increased circulating adrenocorticotropin level ( J:110599 )

• unexpectedly, 4-month-old homozygotes show a 4-fold increase in serum ACTH levels relative to wild-type controls

• increased ACTH levels are due to aberrant processing of the POMC propeptide in melanotrophs, as shown by a 4- to 5-fold increase in expression of prohormone convertase Pcsk1 (PC1) in the intermediate lobe of mutant mice

decreased body temperature ( J:29045 )

• homozygotes exhibit a 0.7 degree C reduction in body temperature relative to wild-type mice

reproductive system

small ovary ( J:29045 )

♀

small testis ( J:29045 )

♂

abnormal estrous cycle ( J:41857 )

♀ • female homozygotes display an abnormal estrous cycle

prolonged diestrus ( J:41857 )

♀ • female homozygotes display a prolonged diestrus, as shown by the continued presence of lymphocytes in vaginal fluid

abnormal estrus ( J:41857 )

♀ • a recognizable estrus is observed only once a month instead of every 4 days

reduced fertility ( J:29045 )

• litters can only be obtained by breeding homozygous mutant mice with their heterozygous counterparts

reduced female fertility ( J:41857 )

♀ • female homozygotes display impaired gonadal function due to hyperprolactinemia

♀ • in contrast, male homozygotes exhibit normal spermatogenesis

nervous system

increased susceptibility to pharmacologically induced seizures ( J:65767 )

• at 10 mg/kg kainic acid (i.p.), homozygotes display preconvulsive behaviors (rigid posture, tail stiffening, and forelimb extension) whereas wild-type and heterozygotes remain immobile

• at 20 mg/kg kainic acid, homozygotes exhibit obvious symptoms of limbic epileptic activity (repeated episodes of rearing with forelimb clonus, alternating with rigid posture and head bobbing), whereas wild-type and heterozygous controls display only preconvulsive signs

• however, at 35 mg/kg kainic acid, homozygotes exhibit repeated limbic seizures of the same severity as those observed in wild-type and heterozygous controls

decreased lactotroph cell size ( J:41857 )

• at 4 months of age, prolactin-positive cells appear smaller and more compact than normal

increased lactotroph cell number ( J:41857 )

• at 4 months of age, female homozygotes show an increased number of lactotrophs relative to wild-type controls

• aberrant proliferation of lactotrophs gives rise to tumors in aged mice

decreased somatotroph cell number ( J:41857 )

• at 4 months of age, female homozygotes show a 25% decrease in the number of GH-expressing cellls relative to wild-type controls

increased thyrotroph cell number ( J:41857 )

• at 4 months of age, female homozygotes show a 2-fold increase in thyrotroph cell number relative to wild-type controls

• however, plasma beta-TSH levels are not significantly increased

adenohypophysis hyperplasia ( J:41857 )

♀ • at 4 months of age, the anterior lobe of female mutant pituitaries shows an increase in both cell number and density relative to that in wild-type controls

enlarged pituitary gland ( J:41857 )

• at 4 months of age, homozygotes of both sexes display an enlarged pituitary

• however, pituitary enlargement is less pronounced in males

pituitary gland hyperplasia ( J:41857 )

• mutant pituitaries show absence of dopaminergic control (sites) resulting in pituitary cell proliferation

• male homozygotes display less prominent pituitary gland hyperplasia than age-matched female homozygotes

• hyperplasia appears to correlate with a progressive induction of prolactin receptor levels in the pituitary gland as homozygotes become older

• whereas hyperplasia of the intermediate lobe occurs earlier (7-8 weeks of age) and remains contained even in aged animals, hyperplasia of the anterior lobe is delayed (3-4 months) but progressive leading to tumors in aged mice

abnormal melanotroph morphology ( J:110599 )

• at 4 months of age, homozygotes display both increased melanotroph proliferation and altered cellular identity

pituitary intermediate lobe hyperplasia ( J:41857 , J:110599 )

• at 4 months of age, intermediate lobe hyperplasia is due to increased proliferation of POMC-producing melanotrophs (J:110599)

♀ • at 4 months of age, the intermediate lobe of female mutant pituitaries shows a 40% increase in cell number, but not in cell density, relative to that in wild-type controls (J:41857)

increased pituitary adenoma incidence ( J:41857 )

• at 8-14 months of age, all female homozygotes display anterior pituitary tumors with nodular areas and large blood vessel infiltration

• male homozygotes develop anterior pituitary tumors much later than female homozygotes (19 months versus 8 months of age, respectively)

abnormal pituitary gland physiology ( J:110599 )

• at 4 months of age, homozygotes show a 2-fold increase in POMC expression that is specifically restricted to pituitary melanotrophs

• mutant melanotrophs lose their cell identity and display aberrant production of ACTH leading to adrenal hyperplasia

• however, expression of the hypothalamic corticotropin releasing hormone (CRF) involved in the regulation of POMC synthesis remains unaffected

abnormal neuron physiology ( J:65767 )

• at 3 hrs after kainic acid treatment (20 mg/kg), homozygotes show a strong and widespread Fos expression throughout the entire brain, whereas wild-type controls display a reduced labeling that is primarily restricted to the hippocampus

• at 6 hrs after kainic acid treatment (20 mg/kg), homozygotes exhibit sustained Fos expression in the hippocampus and cerebral cortex, whereas no labeling is detected in wild-type controls

• at 6 hrs after kainic acid treatment (20 mg/kg), homozygotes, but not wild-type controls, exhibit a robust Jun induction in the dentate gyrus, and hippocampal CA1 nd CA3 regions

increased susceptibility to neuronal excitotoxicity ( J:65767 )

• at 16 hrs after 20 or 35 mg/kg kainic acid administration, homozygotes, but not wild-type controls, display induction of Jun mRNA and the proapoptotic factor BAX, as well as fragmented DNA in CA3 cells and an increased number of TUNEL-positive cells, suggesting hippocampal cell death by apoptosis

• the extension of BAX labeling and tissue damage in the CA3 subfield are larger than that of TUNEL staining, indicating progressive apoptotic hippocampal cell death after kainic acid-induced seizures

• cell loss is detected only in the CA3 subfield but not in other regions of the hippocampus

• an extensive gliosis is observed in the CA3 subfield by GFAP immunohistochemistry

• the extent of CA3 cell damage following treatment with 35 mg/kg kainic acid is greater than that observed with 20 mg/kg, indicating a dose-dependent toxic effect; a higher number of TUNEL-positive cells and a larger extension of reactive gliosis are additionally observed in homozygotes treated with 35 mg/kg

• at 12 hrs after 35 mg/kg kainic acid administration, homozygotes show a stronger Jun induction in the hippocampus and cerebral cortex than wild-type controls, correlating with the occurrence of hippocampal cell death

neoplasm

increased pituitary adenoma incidence ( J:41857 )

• at 8-14 months of age, all female homozygotes display anterior pituitary tumors with nodular areas and large blood vessel infiltration

• male homozygotes develop anterior pituitary tumors much later than female homozygotes (19 months versus 8 months of age, respectively)

pigmentation

hyperpigmentation ( J:110599 )

• at 4 months of age, homozygotes display coat hyperpigmentation due to increased alpha-MSH and ACTH levels

cellular

increased susceptibility to neuronal excitotoxicity ( J:65767 )

• at 16 hrs after 20 or 35 mg/kg kainic acid administration, homozygotes, but not wild-type controls, display induction of Jun mRNA and the proapoptotic factor BAX, as well as fragmented DNA in CA3 cells and an increased number of TUNEL-positive cells, suggesting hippocampal cell death by apoptosis

• the extension of BAX labeling and tissue damage in the CA3 subfield are larger than that of TUNEL staining, indicating progressive apoptotic hippocampal cell death after kainic acid-induced seizures

• cell loss is detected only in the CA3 subfield but not in other regions of the hippocampus

• an extensive gliosis is observed in the CA3 subfield by GFAP immunohistochemistry

• the extent of CA3 cell damage following treatment with 35 mg/kg kainic acid is greater than that observed with 20 mg/kg, indicating a dose-dependent toxic effect; a higher number of TUNEL-positive cells and a larger extension of reactive gliosis are additionally observed in homozygotes treated with 35 mg/kg

• at 12 hrs after 35 mg/kg kainic acid administration, homozygotes show a stronger Jun induction in the hippocampus and cerebral cortex than wild-type controls, correlating with the occurrence of hippocampal cell death

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:29045
primary hyperaldosteronism		DOID:446	OMIM:605635 OMIM:613677	J:110599

Genotype
MGI:3615305

ht3

• Allelic Composition: Drd2^tm1Ebo/Drd2⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

behavior/neurological

abnormal behavior ( J:96229 )

• in a non-selective attention test, mice exhibit higher scanning times (measured by duration of individual rearing episodes) during the first and second part of the test compared with wild-type mice

decreased vertical activity ( J:29045 )

• heterozygotes exhibit a significant reduction in vertical activity (rearing) in the open-field test relative to wild-type mice

decreased locomotor activity ( J:29045 , J:96229 )

• heterozygotes show a significant reduction in locomotion in the open-field test, though of a lesser magnitude than that observed in homozygous mutant mice (J:29045)

• during the first part of the test (J:96229)

catalepsy ( J:29045 )

• heterozygotes display a significant increase in cataleptic-like behavior in the ring test, though of a lesser magnitude than that observed in homozygous mutant mice

Genotype
MGI:4839981

cx4

• Allelic Composition: Drd2^tm1Ebo/Drd2^tm1Ebo; Drd3^tm1Dac/Drd3^tm1Dac
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6

behavior/neurological

abnormal behavior ( J:96229 )

• in a non-selective attention test, mice exhibit lower scanning times (measured by duration of individual rearing episodes) during the first part of the test compared with wild-type mice

abnormal emotion/affect behavior ( J:96229 )

• mice exhibit a reduction in defecation score, as an emotional index, compared with wild-type mice

decreased vertical activity ( J:96229 )

• frequency and duration

decreased locomotor activity ( J:96229 )

digestive/alimentary system

abnormal defecation ( J:96229 )

• mice exhibit a reduction in defecation score, as an emotional index, compared with wild-type mice

Genotype
MGI:4440953

cx5

• Allelic Composition: Drd1^tm1Jcd/Drd1^tm1Jcd; Drd2^tm1Ebo/Drd2⁺
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:91781 )

• mutant mice do not survive the postweaning period unless given highly hydrated food

• when fed a normal breeder diet, only 50% of mutants survive to P25 but none survive to P50

• when fed a semiliquid diet, 86% of mutantss survive to P25 and 69% survive to P50

• however, when the semiliquid feeding regimen is discontinued, mutant mice lose weight and eventually die within 2-3 days

growth/size/body

postnatal growth retardation ( J:91781 )

• mutant mice fed a normal breeder diet fail to thrive after weaning whereas those fed a semiliquid diet grow at a significantly reduced rate relative to wild-type controls

behavior/neurological

abnormal eating behavior ( J:91781 )

digestive/alimentary system

gastrointestinal hemorrhage ( J:91781 )

• at 21 days of age, mutant mice fed with a normal breeder diet display hemorrhages in the digestive tract

intestinal ulcer ( J:91781 )

• mutant mice fed a normal breeder diet display multiple chronic small intestine ulcers accompanied by intense hemorrhage

• however, no ulcers or intense hemorrhage are observed when mutant mice are fed a semiliquid diet

abnormal duodenum morphology ( J:91781 )

• mutant mice fed with breeder diet display a severe villous atrophy in the duodenum

• lethal ulcerations appear to be prevented by a semiliquid diet

abnormal stomach morphology ( J:91781 )

• no food is ever found in mutant stomachs despite food ingestion

small intestinal inflammation ( J:91781 )

• mutant mice fed a normal breeder diet display severe ulcerative jejunoileitis, characterized by multiple chronic small intestine ulcers and bleeding

• histological changes are pronounced in the duodenum and upper jejunum, less prominent in the lower jejunum, and nearly absent in the ileum

immune system

small intestinal inflammation ( J:91781 )

• mutant mice fed a normal breeder diet display severe ulcerative jejunoileitis, characterized by multiple chronic small intestine ulcers and bleeding

• histological changes are pronounced in the duodenum and upper jejunum, less prominent in the lower jejunum, and nearly absent in the ileum

cardiovascular system

gastrointestinal hemorrhage ( J:91781 )

• at 21 days of age, mutant mice fed with a normal breeder diet display hemorrhages in the digestive tract

Genotype
MGI:4440949

cx6

• Allelic Composition: Drd1^tm1Jcd/Drd1^tm1Jcd; Drd2^tm1Ebo/Drd2^tm1Ebo
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:91781 )

• double homozygotes die during the second or third week of life, with none surviving beyond postnatal day 18 (P18)

growth/size/body

decreased body size ( J:91781 )

• double homozygotes appear runted at P11

postnatal growth retardation ( J:91781 )

• double homozygotes fail to thrive after P7-P10

behavior/neurological

aphagia ( J:91781 )

• double homozygotes cease feeding during postnatal development

• hand-feeding initiated at P11 fails to extend survival beyond P15

absent gastric milk in neonates ( J:91781 )

• only traces of milk are detected in double mutant stomachs

decreased locomotor activity ( J:91781 )

• growth arrest is followed by significant hypoactivity

nervous system

nervous system phenotype ( J:91781 )

N • double homozygotes display normal brain morphology and development of dopaminergic and striatal neurons

abnormal hypothalamus physiology ( J:91781 )

• expression of neuropeptide Y (NPY) and agouti-related protein (AGRP) is increased by 3- and 2-fold, respectively, in the arcuate nuclei of double mutant mice

• in contrast, orexin expression in the lateral hypothalamic area is decreased by 40% relative to that in wild-type controls

cardiovascular system

gastrointestinal hemorrhage ( J:91781 )

• at 7-15 days of age, 5 of 45 double homozygotes display hemorrhage in the digestive tract

digestive/alimentary system

abnormal digestive system development ( J:91781 )

• double homozygotes display abnormal development and/or function of the digestive tract

abnormal intestine morphology ( J:91781 )

• double homozygotes show a reduction in intestinal diameter relative to wild-type controls

abnormal intestinal smooth muscle morphology ( J:91781 )

• double homozygotes exhibit poorly formed intestinal smooth muscle cell layers

abnormal digestive system physiology ( J:91781 )

• double homozygotes lack well formed feces in the colon and rectum, suggesting dysregulation of GI motility and water absorption from the large bowel

gastrointestinal hemorrhage ( J:91781 )

• at 7-15 days of age, 5 of 45 double homozygotes display hemorrhage in the digestive tract

muscle

abnormal intestinal smooth muscle morphology ( J:91781 )

• double homozygotes exhibit poorly formed intestinal smooth muscle cell layers

Genotype
MGI:4441067

cx7

• Allelic Composition: Drd1^tm1Jcd/Drd1⁺; Drd2^tm1Ebo/Drd2^tm1Ebo
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6

mortality/aging

mortality/aging ( J:91781 )

N • mutant mice are viable and able to reach adulthood