Phenotypes associated with this allele

• Allele Symbol: Met^tm1Sst
• Allele Name: targeted mutation 1, Snorri S Thorgeirsson
• Allele ID: MGI:3041135
• Summary: 13 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Met^tm1Sst/Met^tm1Sst	involves: 129P2/OlaHsd * C57BL/6	MGI:3041260
cn2	Met^tm1Sst/Met^tm1Sst Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0	involves: 129 * 129P2/OlaHsd * C57BL/6	MGI:4938180
cn3	Met^tm1Sst/Met^tm1Sst Sftpc^tm1(cre/ERT2,rtTA)Hap/Sftpc^+	involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:6197801
cn4	Met^tm1Sst/Met^tm1Sst Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd	MGI:5293779
cn5	Met^tm1Cpo/Met^tm1Sst Tg(Nes-cre)1Kln/?	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL	MGI:5052134
cn6	Met^tm1Cpo/Met^tm1Sst Tg(Nes-cre)1Kln/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5285657
cn7	Met^tm1Sst/Met^tm1Sst Trp53^tm1Brn/Trp53^tm2Tyj	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:5293786
cn8	Met^tm1Sst/Met^tm1Sst Trp53^tm1Brn/Trp53^tm3Tyj	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:5293785
cn9	Met^tm1Sst/Met^tm1Sst Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3041261
cn10	Met^tm1Sst/Met^tm1Sst Tg(Pdx1-cre)89.1Dam/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:5504390
cn11	Met^tm1Sst/Met^tm1Sst Tg(mI56i-cre,EGFP)1Kc/0	involves: 129P2/OlaHsd * C57BL/6J * FVB	MGI:4950068
cn12	Met^tm1Sst/Met^tm1Sst Tg(Nes-cre)1Kln/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:7703099
cn13	Met^tm1Ics/Met^tm1Sst Tg(Nes-cre)1Kln/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5285658

Genotype
MGI:3041260

hm1

• Allelic Composition: Met^tm1Sst/Met^tm1Sst
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

normal phenotype

no abnormal phenotype detected ( J:89236 )

• homozygotes are viable, fertile, grow at a normal rate, and show no histological or physiological abnormalities at >1 year of age

Genotype
MGI:4938180

cn2

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Tg(SFTPC-rtTA)5Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6

respiratory system

abnormal lung development ( J:124125 )

• newborn mice exposed to doxycycline from E14.5 to birth display defective distal lung saccular development due to reduced primary septation

abnormal lung saccule morphology ( J:124125 )

• newborn mice exposed to doxycycline from E14.5 to birth display dilated distal airspaces with only few primary septae, unlike wild-type controls where extensive numbers of saccules are observed

Genotype
MGI:6197801

cn3

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Sftpc^{tm1(cre/ERT2,rtTA)Hap}/Sftpc⁺
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB/N

respiratory system

abnormal pulmonary alveolus morphology ( J:264185 )

• tamoxifen-treated mice show reduced density of alveoli

overexpanded pulmonary alveolus ( J:264185 )

• alveoli are enlarged in tamoxifen-treated mice

emphysema ( J:264185 )

• adult mice treated with tamoxifen exhibit enlargement of alveolar airspace and loss of alveolar density, indicating emphysematous changes

Genotype
MGI:5293779

cn4

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd

cellular

cellular phenotype ( J:175978 )

N • ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit reduced invasion compared with cells from Trp53^tm1Brn homozygotes transfected with a lacZ-expressing adenoviru

Genotype
MGI:5052134

cn5

• Allelic Composition: Met^tm1Cpo/Met^tm1Sst; Tg(Nes-cre)1Kln/?
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL

vision/eye

vision/eye phenotype ( J:173661 )

N • no effect on retinal ganglion cell survival after optic nerve axotomy

Genotype
MGI:5285657

cn6

• Allelic Composition: Met^tm1Cpo/Met^tm1Sst; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

nervous system

abnormal motor neuron innervation pattern ( J:174591 )

• mice exhibit reduced motor axon arborization (length and number of branches) in the pectoralis minor muscle compared with wild-type mice

• at P2, endplates in the pectoralis minor exhibit increased partially or completely denervated synapses compared with wild-type endplates

• however, mice exhibit normal innervation of the pectoralis minor muscle at E15.5 and of the pectoralis major

decreased motor neuron number ( J:174591 )

• by P2 in the C8 and T1 region of the spinal cord with no further reduction in adult mice

abnormal neuromuscular synapse morphology ( J:174591 )

• mice exhibit reduced motor axon arborization (length and number of branches) in the pectoralis minor muscle compared with wild-type mice

• at P2, endplates in the pectoralis minor exhibit increased partially or completely denervated synapses compared with wild-type endplates

• however, mice exhibit normal innervation of the pectoralis minor muscle at E15.5 and of the pectoralis major

behavior/neurological

impaired coordination ( J:174591 )

• in a wire hang test but not a rotarod

Genotype
MGI:5293786

cn7

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Trp53^tm1Brn/Trp53^tm2Tyj
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

cellular

cellular phenotype ( J:175978 )

N • ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit reduced invasion compared with similarly treated cells from Trp53^tm1Brn/Trp53^tm2Tyj mice

Genotype
MGI:5293785

cn8

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Trp53^tm1Brn/Trp53^tm3Tyj
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

cellular

cellular phenotype ( J:175978 )

N • ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit reduced invasion compared with similarly treated cells from Trp53^tm1Brn/Trp53^tm3Tyj mice

Genotype
MGI:3041261

cn9

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

abnormal susceptibility to injury induced morbidity/mortality ( J:89236 )

• mutants are more vulnerable to hepatectomy surgery and most are either moribund or die by 48 hours after surgery

liver/biliary system

liver hemorrhage ( J:89236 )

• mutants develop hemorrhagic liver destruction within the first few hours in response to apoptotic stimuli induced by Fas (Tnfrsf6) antibody compared to only minor liver damage in controls

abnormal hepatocyte physiology ( J:89236 )

• primary hepatocytes show reduced phagocytic activity towards bacteria (E.coli) than control cells

increased hepatocyte apoptosis ( J:89236 )

• hepatocytes exhibit increased sensitivity to Fas (Tnfrsf6)-induced apoptosis

impaired liver regeneration ( J:89236 )

• the ability of mutant livers to clear necrotic tissue and to repopulate the injured (by CCl₄ exposure) area by regenerating hepatocytes is impaired

• associated with a persistent inflammatory reaction, overproduction of osteopontin, early and prominent dystrophic calcification, and impaired hepatocyte scattering/migration into diseased areas

liver failure ( J:89236 )

• 80% of mutants die of acute liver failure in response to apoptotic stimuli induced by Fas (Tnfrsf6) antibody while controls survive

cardiovascular system

liver hemorrhage ( J:89236 )

• mutants develop hemorrhagic liver destruction within the first few hours in response to apoptotic stimuli induced by Fas (Tnfrsf6) antibody compared to only minor liver damage in controls

homeostasis/metabolism

abnormal response to injury ( J:89236 )

• mutants exhibit delayed healing after toxic liver injury induced by CCl₄ exposure

abnormal susceptibility to injury induced morbidity/mortality ( J:89236 )

• mutants are more vulnerable to hepatectomy surgery and most are either moribund or die by 48 hours after surgery

impaired wound healing ( J:89236 )

• hepatocytes fail to migrate in a standard wound healing assay

cellular

increased hepatocyte apoptosis ( J:89236 )

• hepatocytes exhibit increased sensitivity to Fas (Tnfrsf6)-induced apoptosis

Genotype
MGI:5504390

cn10

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:196854 )

♀ • islets from pregnant mutants do not exhibit an increase in insulin content as seen in pregnant wild-type females

decreased pancreatic beta cell mass ( J:196854 )

♀ • pregnant females show decreased beta cell mass at gestational day 19 compared to controls, at a time when maximal beta-cell mass expansion occurs during pregnancy

♀ • the decrease in beta-cell mass persists at postpartum day 4

♀ • however, islet number and beta-cell size are similar to wild-type at gestational day 19

abnormal pancreatic beta cell physiology ( J:196854 )

♀ • apoptosis in beta-cells of mutant pregnant females is premature and is increased at gestational day 15, however at gestational day 19 and postpartum day 4, beta cell apoptosis is increased similarly in wild-type and mutant pregnant females

♀ • mutant beta cells are more sensitive to the cytotoxic effects of a low dose of the synthetic hormone dexamethasone that does not induce cell death in wild-type islets

decreased pancreatic beta cell proliferation ( J:196854 )

♀ • pregnant females show a decrease in beta-cell proliferation at gestational day 15, when maximal beta-cell proliferation normally occurs during pregnancy

♀ • beta-cell proliferation is also decreased at postpartum day 4

♀ • however, beta-cell proliferation is similar to wild-type at gestational day 11 and 19

decreased insulin secretion ( J:196854 )

♀ • islets from pregnant mutants do not exhibit an increase in insulin content as seen in pregnant wild-type females

♀ • islets from mutant pregnant females do not exhibit an increase in glucose-stimulated insulin secretion at gestational day 19 that is seen in wild-type pregnant females

homeostasis/metabolism

decreased insulin secretion ( J:196854 )

♀ • islets from pregnant mutants do not exhibit an increase in insulin content as seen in pregnant wild-type females

♀ • islets from mutant pregnant females do not exhibit an increase in glucose-stimulated insulin secretion at gestational day 19 that is seen in wild-type pregnant females

increased circulating glucose level ( J:196854 )

♀ • blood glucose is higher in pregnant mutant females at gestational day 19 than in wild-type pregnant females

♀ • fasting blood glucose is increased in pregnant mutant females at gestational day 19 than in wild-type pregnant females

decreased circulating insulin level ( J:196854 )

♀ • plasma insulin levels are diminished in pregnant mutant females at gestational day 19 compared to wild-type pregnant females

impaired glucose tolerance ( J:196854 )

♀ • glucose tolerance is impaired more in pregnant mutant females than pregnant wild-type females at gestational day 15 and 19 and at postpartum day 4

♀ • pregnant mutant females respond similarly to insulin tolerance tests at gestational day 18 as wild-type females, indicating that enhanced impairment in glucose tolerance is not related to changes in insulin sensitivity

cellular

decreased pancreatic beta cell proliferation ( J:196854 )

♀ • pregnant females show a decrease in beta-cell proliferation at gestational day 15, when maximal beta-cell proliferation normally occurs during pregnancy

♀ • beta-cell proliferation is also decreased at postpartum day 4

♀ • however, beta-cell proliferation is similar to wild-type at gestational day 11 and 19

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
gestational diabetes		DOID:11714		J:196854

Genotype
MGI:4950068

cn11

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Tg(mI56i-cre,EGFP)1Kc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB

behavior/neurological

behavior/neurological phenotype ( J:170554 )

N • in the Morris water maze, mutants have a longer latency to locate the platform on the first 2 days of training than controls, however performance on the probe test and reversal probe test were normal, indicating normal hippocampal-mediated spatial learning

N • open field activity and anxiety are not affected

abnormal learning/memory/conditioning ( J:170554 )

• on reversal discriminations, mutants require more trials than controls, indicating impaired reversal learning

impaired cued conditioning behavior ( J:170554 )

• mutants show increased latency performance on the cued-platform test, indicating a delay in striatal-dependent cued learning

nervous system

abnormal brain interneuron morphology ( J:170554 )

• marker analysis indicates an increase in numbers of PV+ and SST+ striatal GABAergic interneurons

• distribution of striatal interneurons is altered, with fewer cells of the population located in the medial (associative) regions and more cells in the lateral (sensorimotor) areas

• reduction in the numbers of PV+ GABAergic interneurons in the primary somatosensory cortex (28% loss) and the orbitofrontal cortex (31% loss)

abnormal striatum morphology ( J:170554 )

• marker analysis indicates an increase in numbers of PV+ and SST+ striatal GABAergic interneurons

• however, striatum appears normal

abnormal orbitofrontal cortex morphology ( J:170554 )

• 31% reduction in PV+ cells in the orbitofrontal cortex

abnormal primary somatosensory cortex morphology ( J:170554 )

• 28% loss of PV+ cells in primary somatosensory cortex

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:170554
Gilles de la Tourette syndrome		DOID:11119	OMIM:137580	J:170554

Genotype
MGI:7703099

cn12

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

nervous system

abnormal cerebral cortex morphology ( J:351261 )

• increased FOS+ infragranular neurons in the medial prefrontal cortex of male and female mice at P90 compared with controls

• however, FOS+ cells are normal in number at P35 during fear memory expression

behavior/neurological

impaired contextual conditioning behavior ( J:351261 )

♀ • at P90 in female mice

♀ • however, female and male mice exhibit normal contextual fear memory formation and persistence at P23 as well as contextual remote fear memory at P35 and 50

Genotype
MGI:5285658

cn13

• Allelic Composition: Met^tm1Ics/Met^tm1Sst; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

nervous system

decreased motor neuron number ( J:174591 )

• by P2 with no further reduction in adult mice

• lacZ+ motor neurons are reduced at P2 in C8 and T1 regions of the spinal cord