Phenotypes associated with this allele

• Allele Symbol: Th^tm1(cre)Te
• Allele Name: targeted mutation 1, Ted Ebendal
• Allele ID: MGI:3056580
• Summary: 12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Th^tm1(cre)Te/Th^tm1(cre)Te	involves: 129X1/SvJ * C57BL/6J	MGI:3718062
cn2	Sdhd^tm1Jlob/Sdhd^tm2Jlob Th^tm1(cre)Te/Th^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5438130
cn3	Slc17a6^tm1Kldr/Slc17a6^tm1Kldr Th^tm1(cre)Te/Th^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4887826
cn4	Grpr^tm1Jfb/Grpr^tm1Jfb Slc17a6^tm1Kldr/Slc17a6^tm1Kldr Th^tm1(cre)Te/Th^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4887830
cn5	Ndufa4l2^tm1.1Jlob/Ndufa4l2^tm1.2Jlob Th^tm1(cre)Te/Th^+	involves: 129S/Sv * 129X1/SvJ * C57BL/6NCrl * C57BL/6NTac	MGI:6724163
cn6	Cox4i2^tm1Hutt/Cox4i2^tm1.1Jlob Th^tm1(cre)Te/Th^+	involves: 129X1/SvJ * C57BL/6	MGI:6724164
cn7	Or51e2^tm3.1Mom/Or51e2^tm3.1Mom Th^tm1(cre)Te/?	involves: 129X1/SvJ * C57BL/6	MGI:7663959
cn8	Tg(CAG-Alk*F1174L,-luc)60Jhsc/0 Th^tm1(cre)Te/Th^+	involves: 129X1/SvJ * C57BL/6 * FVB/N	MGI:6196045
cn9	Med22^tm1a(EUCOMM)Hmgu/Med22^tm1a(EUCOMM)Hmgu Th^tm1(cre)Te/Th^+	involves: 129X1/SvJ * C57BL/6N	MGI:6509609
cn10	Med22^tm1a(EUCOMM)Hmgu/Med22^+ Th^tm1(cre)Te/Th^+	involves: 129X1/SvJ * C57BL/6N	MGI:6509610
cn11	Psmc1^tm1Maye/Psmc1^tm1.1Maye Th^tm1(cre)Te/Th^+	involves: 129X1/SvJ * CD-1	MGI:3809797
cn12	Psmc1^tm1Maye/Psmc1^tm1Maye Th^tm1(cre)Te/Th^+	involves: 129X1/SvJ * CD-1	MGI:3809774

Genotype
MGI:3718062

hm1

• Allelic Composition: Th^tm1(cre)Te/Th^tm1(cre)Te
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

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

normal phenotype

no abnormal phenotype detected ( J:93194 )

• mice are viable and fertile with normal body weight, spontaneous movement, and rotarod performance

Genotype
MGI:5438130

cn2

• Allelic Composition: Sdhd^tm1Jlob/Sdhd^tm2Jlob; Th^tm1(cre)Te/Th⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:186713 )

• most mice die before the first year of age

nervous system

abnormal adrenal chromaffin cell morphology ( J:186713 )

• adrenal medulla chromaffin cells exhibit decreased intracellular ATP compared with wild-type cells

• mice exhibit a decrease in catecholaminergic cells compared with wild-type mice

abnormal dopaminergic neuron morphology ( J:186713 )

• exhibit impaired maturation and accelerated degeneration of dopaminergic cells, aggressively in the substantia nigra pars compacta, compared with wild-type mice

loss of dopaminergic neurons ( J:186713 )

decreased neuron number ( J:186713 )

• mice exhibit decreased neuron numbers in the adrenal medulla, carotid body and superior cervical ganglion compared with wild-type mice

• mice exhibit a decrease in catecholaminergic cells compared with wild-type mice

• progressive reduction in the ventral mesencephalic TH+ neurons with almost complete disappearance of neurons between 6 and 12 months

• neurons loss is less severe in the ventral tegmental area

• however, treatment with an antioxidant in the drinking water rescues neuron survival

behavior/neurological

decreased locomotor activity ( J:186713 )

• progressive bradykinetic syndrome with decreased distance traveled in the open field and increase in time spent at rest

bradykinesia ( J:186713 )

• progressive bradykinetic syndrome with decreased distance traveled in the open field and increase in time spent at rest

endocrine/exocrine glands

abnormal adrenal chromaffin cell morphology ( J:186713 )

• adrenal medulla chromaffin cells exhibit decreased intracellular ATP compared with wild-type cells

• mice exhibit a decrease in catecholaminergic cells compared with wild-type mice

homeostasis/metabolism

decreased dopamine level ( J:186713 )

• at 2.5 months, mice fail to exhibit an increase in dopamine and its metabolites unlike in wild-type mice

cellular

oxidative stress ( J:186713 )

• increased lipid peroxidation in the adrenal medulla

growth/size/body

decreased birth body size ( J:186713 )

neoplasm

neoplasm ( J:186713 )

N • mice do not develop tumors

Genotype
MGI:4887826

cn3

• Allelic Composition: Slc17a6^tm1Kldr/Slc17a6^tm1Kldr; Th^tm1(cre)Te/Th⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological

excessive scratching ( J:167752 )

abnormal pain threshold ( J:167752 )

• mice display decreased responsiveness to radiant heat but response to mechanically-induced pain is not significantly different from wild-type controls

decreased chemically-elicited antinociception ( J:167752 )

• mice have decreased sensitivity to inflammatory pain induced by formalin injection, but response to mechanically-induced pain is not different from wild-type

increased thermal nociceptive threshold ( J:167752 )

• latency of withdrawal in hot plate tests is significantly greater than wild-type at both 52 and 48 degrees

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:167752 )

N • plasma creatinine, urea, and tyroxine 4 levels are normal, with slightly elevated by still within normal range levels of alanine aminotransferase; this excludes a systemic disorder (chronic itch) as underlying the elevated scratching

integument

mixed cellular infiltration to dermis ( J:167752 )

• immune cells are found in the dermis in wounded areas indicative of prolonged scratching and rubbing

thick epidermis ( J:167752 )

• mice display thickened epidermis of psoriasiform type in wounded areas

skin lesions ( J:167752 )

• mice develop lesions (ulcerations) in the neck and upper back region

increased pruritus ( J:167752 )

• mice display a chronic itch behavior (display frequent scratching episodes)

• topical application of a histamine receptor antagonist significantly reduces scratching behavior; oral administration of a blood-brain barrier impermeant antihistamine causes a similar reduction in scratching

• topical administration of capsaicin reduces the itch phenotype

Genotype
MGI:4887830

cn4

• Allelic Composition: Grpr^tm1Jfb/Grpr^tm1Jfb; Slc17a6^tm1Kldr/Slc17a6^tm1Kldr; Th^tm1(cre)Te/Th⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological

excessive scratching ( J:167752 )

♀ • compound mutant mice show elevated scratching compared to wild-type but this is significantly reduced from that shown by mutants with intact Grpr function

Genotype
MGI:6724163

cn5

• Allelic Composition: Ndufa4l2^tm1.1Jlob/Ndufa4l2^tm1.2Jlob; Th^tm1(cre)Te/Th⁺
• Genetic Background: involves: 129S/Sv * 129X1/SvJ * C57BL/6NCrl * C57BL/6NTac

homeostasis/metabolism

abnormal physiological response to hypoxia ( J:302384 )

• slightly higher responsiveness to hypoxia

• however, mice exhibit normal ventilatory responses to hypoxia and hypercapnia

Genotype
MGI:6724164

cn6

• Allelic Composition: Cox4i2^tm1Hutt/Cox4i2^tm1.1Jlob; Th^tm1(cre)Te/Th⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6

homeostasis/metabolism

abnormal physiological response to hypoxia ( J:302384 )

• loss of acute responsiveness to hypoxia with decreased glomus cells exhibiting increased cytosolic calcium ions and catecholamine release, and decreased mitochondrial responses to hypoxia

• however, mitochondria complex IV function is normal and ventilatory response to hypercapnia is normal

Genotype
MGI:7663959

cn7

• Allelic Composition: Or51e2^tm3.1Mom/Or51e2^tm3.1Mom; Th^tm1(cre)Te/?
• Genetic Background: involves: 129X1/SvJ * C57BL/6

cardiovascular system

abnormal type I cell of carotid body physiology ( J:350385 )

• these mice have normal hypoxic ventilatory response, but glomus cells have decreased quantal dopamine content, decreased secretory activity in response to hypoxia or hypoglycemia, decreased mean charge per exocytotic vessel, and altered cytosolic calcium dynamics.

nervous system

abnormal type I cell of carotid body physiology ( J:350385 )

• these mice have normal hypoxic ventilatory response, but glomus cells have decreased quantal dopamine content, decreased secretory activity in response to hypoxia or hypoglycemia, decreased mean charge per exocytotic vessel, and altered cytosolic calcium dynamics.

Genotype
MGI:6196045

cn8

• Allelic Composition: Tg(CAG-Alk*F1174L,-luc)60Jhsc/0; Th^tm1(cre)Te/Th⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * FVB/N

neoplasm

increased metastatic potential ( J:186696 )

• extensive liver metastases is seen in some mice

increased neuroblastoma incidence ( J:186696 )

• a low number of mice develop palpable neural crest-derived tumors between 130 and 351 days of age resembling neuroblastomas

• tumors form in the neck or abdomen

• the retroperitoneal tumors originate from the adrenal gland

• tumors consist of poorly differentiated cells with large nuclei and sparse neuropil

• neuroblastomas exhibit chromosomal aberrations recapitulating genomic aberrations of human neuroblastomas

endocrine/exocrine glands

adrenal gland hyperplasia ( J:186696 )

• some adrenals appear hypertrophic in mice that do not develop tumors

nervous system

increased neuroblastoma incidence ( J:186696 )

• a low number of mice develop palpable neural crest-derived tumors between 130 and 351 days of age resembling neuroblastomas

• tumors form in the neck or abdomen

• the retroperitoneal tumors originate from the adrenal gland

• tumors consist of poorly differentiated cells with large nuclei and sparse neuropil

• neuroblastomas exhibit chromosomal aberrations recapitulating genomic aberrations of human neuroblastomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:186696

Genotype
MGI:6509609

cn9

• Allelic Composition: Med22^{tm1a(EUCOMM)Hmgu}/Med22^{tm1a(EUCOMM)Hmgu}; Th^tm1(cre)Te/Th⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6N
• Cell Lines: HEPD0884_4_E12

mortality/aging

preweaning lethality, complete penetrance ( J:300239 )

• no homozygous mice are produced from breeding heterozygotes, suggesting embryonic lethality; time of death not specified

Genotype
MGI:6509610

cn10

• Allelic Composition: Med22^{tm1a(EUCOMM)Hmgu}/Med22⁺; Th^tm1(cre)Te/Th⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6N
• Cell Lines: HEPD0884_4_E12

renal/urinary system

renal/urinary system phenotype ( J:300239 )

N • adult heterozygotes show no renal histological abnormalities up to 15 months of age; albuminuria (as measured by urine albumin/creatinine ratios), glomerulus basement membrane (GBM) thickness, and foot process width (as measured by slits/GBM length) are similar to those in control mice

Genotype
MGI:3809797

cn11

• Allelic Composition: Psmc1^tm1Maye/Psmc1^tm1.1Maye; Th^tm1(cre)Te/Th⁺
• Genetic Background: involves: 129X1/SvJ * CD-1

mortality/aging

postnatal lethality ( J:138991 )

• phenotype is identical to the mouse having Psmc1^tm1Maye/Psmc1^tm1.1Maye; Th^tm1(cre)Te/Th⁺

growth/size/body

decreased body size ( J:138991 )

nervous system

gliosis ( J:138991 )

neuron degeneration ( J:138991 )

alpha-synuclein inclusion body ( J:138991 )

homeostasis/metabolism

decreased dopamine level ( J:138991 )

abnormal noradrenaline level ( J:138991 )

Genotype
MGI:3809774

cn12

• Allelic Composition: Psmc1^tm1Maye/Psmc1^tm1Maye; Th^tm1(cre)Te/Th⁺
• Genetic Background: involves: 129X1/SvJ * CD-1

mortality/aging

postnatal lethality, complete penetrance ( J:138991 )

• die before day 28

growth/size/body

decreased body size ( J:138991 )

• progressively runty from approximately day 14

nervous system

gliosis ( J:138991 )

• extensive gliosis as a result of the neuronal damage

neuron degeneration ( J:138991 )

• progressive degeneration and consequent loss of neuronal projections to the basal ganglia

alpha-synuclein inclusion body ( J:138991 )

• numerous eosinophilic intraneuronal paranuclear inclusions, containing ubiquitin, alpha-synuclein, and p62, similar to Lewy bodies in nigral neurons

homeostasis/metabolism

decreased dopamine level ( J:138991 )

• decreased dopamine and norepinephrine in the striatum and hypothalamus

abnormal noradrenaline level ( J:138991 )

• decreased dopamine and norepinephrine in the striatum and hypothalamus

• decreased norepinephrine in the hippocampus and brainstem