Phenotypes associated with this allele

• Allele Symbol: Dusp1^tm1Brv
• Allele Name: targeted mutation 1, Rodrigo Bravo
• Allele ID: MGI:2667529
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dusp1^tm1Brv/Dusp1^tm1Brv	B6.129S2-Dusp1^tm1Brv	MGI:4940296
hm2	Dusp1^tm1Brv/Dusp1^tm1Brv	C3.129S2-Dusp1^tm1Brv	MGI:4940300
hm3	Dusp1^tm1Brv/Dusp1^tm1Brv	involves: 129S2/SvPas	MGI:2667530
hm4	Dusp1^tm1Brv/Dusp1^tm1Brv	involves: 129S2/SvPas * C57BL/6	MGI:4940244
hm5	Dusp1^tm1Brv/Dusp1^tm1Brv	involves: 129S2/SvPas * various	MGI:4940291
cx6	Dmd^mdx/Dmd^mdx Dusp1^tm1Brv/Dusp1^tm1Brv	involves: 129S2/SvPas * C57BL/6 * C57BL/10ScSn	MGI:4940318

Genotype
MGI:4940296

hm1

• Allelic Composition: Dusp1^tm1Brv/Dusp1^tm1Brv
• Genetic Background: B6.129S2-Dusp1^tm1Brv

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

nervous system

increased neuron apoptosis ( J:163234 )

• at P1, mice exhibit a 3-fold increase in apoptosis within the superior cervical ganglia compared with wild-type mice

abnormal superior cervical ganglion morphology ( J:163234 )

• at P1, mice exhibit fewer sympathetic neurons in the superior cervical ganglion compared with wild-type mice

cellular

increased neuron apoptosis ( J:163234 )

• at P1, mice exhibit a 3-fold increase in apoptosis within the superior cervical ganglia compared with wild-type mice

Genotype
MGI:4940300

hm2

• Allelic Composition: Dusp1^tm1Brv/Dusp1^tm1Brv
• Genetic Background: C3.129S2-Dusp1^tm1Brv

immune system

increased granulocyte number ( J:164929 )

• in the lungs following C. pneumoniae infection

abnormal chemokine secretion ( J:164929 )

• C. pneumoniae-infected mice exhibit increased chemokine levels in lung homogenates (CCL3, CCL4, CXCL1, and CXCL2) compared with similarly treated wild-type mice

increased interleukin-1 beta secretion ( J:164929 )

• in C. pneumoniae-infected mice

increased interleukin-6 secretion ( J:164929 )

• in C. pneumoniae-infected mice

lung inflammation ( J:164929 )

• C. pneumoniae-infected mice exhibit increased pulmonary inflammation and acute bronchopneumia with more pronounced destruction of lung parenchyma compared with similarly treated wild-type mice

increased susceptibility to bacterial infection ( J:164929 )

• C. pneumoniae-infected mice exhibit increased pulmonary inflammation, acute bronchopneumia with more pronounced destruction of lung parenchyma, chemokine levels in lung homogenates (CCL3, CCL4, CXCL1, and CXCL2), IL1b and IL6 secretion, granulocytes in the lungs, weight loss, and pulmonary chlamydial load compared with similarly treated wild-type mice

• however, blockage of IL6 trans-signaling corrects hyperinflammation and increased chlamydial load

respiratory system

lung inflammation ( J:164929 )

• C. pneumoniae-infected mice exhibit increased pulmonary inflammation and acute bronchopneumia with more pronounced destruction of lung parenchyma compared with similarly treated wild-type mice

growth/size/body

weight loss ( J:164929 )

• in C. pneumoniae-infected mice

hematopoietic system

increased granulocyte number ( J:164929 )

• in the lungs following C. pneumoniae infection

Genotype
MGI:2667530

hm3

• Allelic Composition: Dusp1^tm1Brv/Dusp1^tm1Brv
• Genetic Background: involves: 129S2/SvPas

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:118832 )

• in response to intraperitoneal injection of LPS, mortality is observed initially at 22 hours and 83% of the mice are dead at 34 hours whereas mortality is observed first at 34 hours in wild-type and only 25% mortality by 120 hours is seen

homeostasis/metabolism

increased blood urea nitrogen level ( J:118832 )

abnormal circulating alanine transaminase level ( J:118832 )

• levels are increased (149.2 U/L) after LPS injection compared to treated wild-type (22.7 U/L)

pulmonary edema ( J:118832 )

• observed after LPS treatment

abnormal nitric oxide homeostasis ( J:118832 )

• plasma nitrate levels after LPS challenge are elevated in mutants suggesting defective regulation of vascular function by by nitric oxide

cardiovascular system

decreased systemic arterial systolic blood pressure ( J:118832 )

hypotension ( J:118832 )

• LPS (1.5 mg/kg body weight) challenge results in decreased blood pressure in mutants but not in wild-type

immune system

abnormal cytokine secretion ( J:118832 )

• thioglycollate-elicited peritoneal macrophages produce more TNF alpha in response to LPS stimulation; Il-6 production is also significantly elevated

• Il-12 production is decreased in response to LPS stimulation in peritoneal macrophages

• splenocytes stimulated with LPS produce more TNF alpha compared to wild-type but Il-12 and IFN gamma production is attenuated with respect to wild-type

• mutant mice stimulated with LPS in vivo show 3.5-fold higher TNF alpha levels than wild-type at 1 hour and levels still increase at 2 hours; mice produce more Il-6 at 1 hour and this keeps increasing through 3 hours, while Il-10 levels increase and remain elevated throughout the experiment

lung inflammation ( J:118832 )

• massive infiltration of leukocytes is observed after LPS challenge

respiratory system

pulmonary edema ( J:118832 )

• observed after LPS treatment

lung inflammation ( J:118832 )

• massive infiltration of leukocytes is observed after LPS challenge

thick pulmonary interalveolar septum ( J:118832 )

• after LPS challenge, thickened alveolar septa are seen in mutant lungs

Genotype
MGI:4940244

hm4

• Allelic Composition: Dusp1^tm1Brv/Dusp1^tm1Brv
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:118833 )

• LPS-treated mice exhibit increased lethality compared with similarly treated wild-type mice

immune system

increased circulating interleukin-10 level ( J:118833 )

• in LPS-treated mice

increased circulating interleukin-6 level ( J:118833 )

• in LPS-treated mice

increased circulating tumor necrosis factor level ( J:118833 )

• in LPS-treated mice

increased interleukin-6 secretion ( J:118833 )

• from bone marrow-derived macrophages in response to LPS

increased tumor necrosis factor secretion ( J:118833 )

• from bone marrow-derived macrophages in response to LPS

increased susceptibility to endotoxin shock ( J:118833 )

• LPS-treated mice exhibit increased lethality and cytokine production (TNF-alpha and IL6) compared with similarly treated wild-type mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:129718 )

N • mice fed a high-fat diet exhibit normal glucose intolerance

decreased circulating cholesterol level ( J:129718 )

• in mice fed a high-fat diet

decreased circulating free fatty acids level ( J:129718 )

• in mice fed standard chow

decreased circulating triglyceride level ( J:129718 )

• in mice fed standard chow

increased circulating interleukin-10 level ( J:118833 )

• in LPS-treated mice

increased circulating interleukin-6 level ( J:118833 )

• in LPS-treated mice

increased circulating tumor necrosis factor level ( J:118833 )

• in LPS-treated mice

increased energy expenditure ( J:129718 )

• in mice fed a high-fat diet

decreased susceptibility to diet-induced obesity ( J:129718 )

• when fed a high-fat diet

increased respiratory quotient ( J:129718 )

• in mice fed a high-fat diet

increased hepatic glucose production ( J:129718 )

• basal hepatic glucose production is increased compared to in wild-type mice

• however, non-oxidative glucose metabolism is normal

increased susceptibility to xenobiotic induced morbidity/mortality ( J:118833 )

• LPS-treated mice exhibit increased lethality compared with similarly treated wild-type mice

adipose tissue

decreased total body fat amount ( J:129718 )

• in mice fed standard chow or a high-fat diet

decreased fat cell size ( J:129718 )

decreased epididymal fat pad weight ( J:129718 )

decreased abdominal fat pad weight ( J:129718 )

• in mice fed standard chow or a high-fat diet

behavior/neurological

abnormal eating behavior ( J:129718 )

• in mice fed a high-fat diet

abnormal depression-related behavior ( J:166162 )

• mice are resistant to stress-induced anhedonia caused by exposure to chronic unpredictable stress unlike similarly treated wild-type mice

decreased anxiety-related response ( J:166162 )

• mice exposure to chronic unpredictable stress spend more time in the open arms of an elevated plus maze compared with similarly treated wild-type mice

abnormal locomotor activation ( J:129718 )

• mice fed a high-fat diet maintain their activity level unlike similarly treated wild-type mice

muscle

abnormal muscle development ( J:162340 )

• myoblasts exhibit decreased entry into S phase compared with wild-type cells

abnormal myoblast differentiation ( J:162340 )

• myoblasts exhibit precocious myogenesis unlike wild-type cells

• however, treatment with SB203580 (p38alpha/beta MAPK inhibitor) inhibits precocious differentiation

decreased myoblast proliferation ( J:162340 )

• myoblasts from CTX-treated mice exhibit reduced proliferation compared with myoblasts from similarly treated wild-type mice

decreased skeletal muscle fiber size ( J:162340 )

• following CTX treatment

decreased skeletal muscle fiber diameter ( J:162340 )

• following CTX treatment

abnormal muscle regeneration ( J:162340 )

• CTX-treated mice exhibit impaired or delayed muscle regeneration compared with similarly treated wild-type mice

growth/size/body

decreased body weight ( J:129718 )

• after weaning, whether mice are fed standard chow or a high-fat diet

decreased susceptibility to age related obesity ( J:129718 )

decreased susceptibility to diet-induced obesity ( J:129718 )

• when fed a high-fat diet

liver/biliary system

small liver ( J:129718 )

• in aged mice

decreased liver weight ( J:129718 )

• in aged mice on standard chow

• in mice fed a high-fat diet

decreased susceptibility to age-related hepatic steatosis ( J:129718 )

• in aged mice on standard chow

decreased susceptibility to diet-induced hepatic steatosis ( J:129718 )

• in mice fed a high-fat diet

nervous system

abnormal dendrite morphology ( J:166927 )

• BDNF-stimulated neurons fail to exhibit an increase in axonal branches unlike similarly treated wild-type neurons

cellular

abnormal myoblast differentiation ( J:162340 )

• myoblasts exhibit precocious myogenesis unlike wild-type cells

• however, treatment with SB203580 (p38alpha/beta MAPK inhibitor) inhibits precocious differentiation

decreased myoblast proliferation ( J:162340 )

• myoblasts from CTX-treated mice exhibit reduced proliferation compared with myoblasts from similarly treated wild-type mice

abnormal cellular respiration ( J:129718 )

• mitochondria in skeletal muscles exhibit increased respiration compared with wild-type mitochondria

Genotype
MGI:4940291

hm5

• Allelic Composition: Dusp1^tm1Brv/Dusp1^tm1Brv
• Genetic Background: involves: 129S2/SvPas * various

immune system

immune system phenotype ( J:125919 )

N • anti-inflammatory action of glucocorticoids is normal

increased mast cell degranulation ( J:125919 )

• partially reversible by dexamethasone treatment

increased susceptibility to type I hypersensitivity reaction ( J:125919 )

• following injection of dinitrophenyl-human serum albumin (DNP-HSA), mice exhibit a greater reduction in body temperature compared with wild-type mice

• however, pretreatment with dexamethasone restores normal response

homeostasis/metabolism

decreased body temperature ( J:125919 )

• following injection of dinitrophenyl-human serum albumin (DNP-HSA), mice exhibit a greater reduction in body temperature compared with wild-type mice

• however, pretreatment with dexamethasone restores normal response

hematopoietic system

increased mast cell degranulation ( J:125919 )

• partially reversible by dexamethasone treatment

cellular

increased mast cell degranulation ( J:125919 )

• partially reversible by dexamethasone treatment

Genotype
MGI:4940318

cx6

• Allelic Composition: Dmd^mdx/Dmd^mdx; Dusp1^tm1Brv/Dusp1^tm1Brv
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * C57BL/10ScSn

muscle

myositis ( J:162340 )

♀ • mice exhibit enhanced inflammatory response in skeletal muscles compared with Dmd^mdx homozygotes

decreased skeletal muscle fiber size ( J:162340 )

♀ • compared with Dmd^mdx homozygotes

decreased skeletal muscle fiber diameter ( J:162340 )

♀ • compared with Dmd^mdx homozygotes

skeletal muscle fiber degeneration ( J:162340 )

♀ • increased compared to in Dmd^mdx homozygotes

decreased skeletal muscle weight ( J:162340 )

♀ • in the tibialis anterior and gastrocnemius compared with Dmd^mdx homozygotes

dystrophic muscle ( J:162340 )

♀ • mice exhibit an exacerbated dystrophic phenotype compared with Dmd^mdx homozygotes

immune system

myositis ( J:162340 )

♀ • mice exhibit enhanced inflammatory response in skeletal muscles compared with Dmd^mdx homozygotes

behavior/neurological

decreased grip strength ( J:162340 )

♀ • compared with Dmd^mdx homozygotes

growth/size/body

decreased body size ( J:162340 )

♀ • at 8 weeks compared with Dmd^mdx homozygotes

decreased body weight ( J:162340 )

♀ • at 8 weeks compared with Dmd^mdx homozygotes