Mouse Genome Informatics
hm1
    Mettm1Sst/Mettm1Sst
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• homozygotes are viable, fertile, grow at a normal rate, and show no histological or physiological abnormalities at >1 year of age


Mouse Genome Informatics
cn2
    Mettm1Sst/Mettm1Sst
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-cre)1Jaw/0

involves: 129 * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• newborn mice exposed to doxycycline from E14.5 to birth display defective distal lung saccular development due to reduced primary septation
• 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


Mouse Genome Informatics
cn3
    Mettm1Sst/Mettm1Sst
Trp53tm1Brn/Trp53tm1Brn

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
N
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit reduced invasion compared with cells from Trp53tm1Brn homozygotes transfected with a lacZ-expressing adenoviru (J:175978)


Mouse Genome Informatics
cn4
    Mettm1Cpo/Mettm1Sst
Tg(Nes-cre)1Kln/?

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
N
• no effect on retinal ganglion cell survival after optic nerve axotomy (J:173661)


Mouse Genome Informatics
cn5
    Mettm1Cpo/Mettm1Sst
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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
• by P2 in the C8 and T1 region of the spinal cord with no further reduction in adult mice
• 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
• in a wire hang test but not a rotarod


Mouse Genome Informatics
cn6
    Mettm1Sst/Mettm1Sst
Trp53tm1Brn/Trp53tm3Tyj

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
N
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit reduced invasion compared with similarly treated cells from Trp53tm1Brn/Trp53tm3Tyj mice (J:175978)


Mouse Genome Informatics
cn7
    Mettm1Sst/Mettm1Sst
Trp53tm1Brn/Trp53tm2Tyj

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
N
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit reduced invasion compared with similarly treated cells from Trp53tm1Brn/Trp53tm2Tyj mice (J:175978)


Mouse Genome Informatics
cn8
    Mettm1Sst/Mettm1Sst
Tg(Alb-cre)21Mgn/0

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
liver/biliary system
• 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
• primary hepatocytes show reduced phagocytic activity towards bacteria (E.coli) than control cells
• hepatocytes exhibit increased sensitivity to Fas (Tnfrsf6)-induced apoptosis
• 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
• 80% of mutants die of acute liver failure in response to apoptotic stimuli induced by Fas (Tnfrsf6) antibody while controls survive

cardiovascular system
• 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
• mutants exhibit delayed healing after toxic liver injury induced by CCl4 exposure
• mutants are more vulnerable to hepatectomy surgery and most are either moribund or die by 48 hours after surgery
• hepatocytes fail to migrate in a standard wound healing assay

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


Mouse Genome Informatics
cn9
    Mettm1Sst/Mettm1Sst
Tg(Pdx1-cre)89.1Dam/0

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• islets from pregnant mutants do not exhibit an increase in insulin content as seen in pregnant wild-type females (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 (J:196854)
• the decrease in beta-cell mass persists at postpartum day 4 (J:196854)
• however, islet number and beta-cell size are similar to wild-type at gestational day 19 (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 (J:196854)
• 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 (J:196854)
• beta-cell proliferation is also decreased at postpartum day 4 (J:196854)
• pregnant females show a decrease in beta-cell proliferation at gestational day 15, when maximal beta-cell proliferation normally occurs during pregnancy (J:196854)
• however, beta-cell proliferation is similar to wild-type at gestational day 11 and 19 (J:196854)
• islets from pregnant mutants do not exhibit an increase in insulin content as seen in pregnant wild-type females (J:196854)
• 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 (J:196854)

homeostasis/metabolism
• islets from pregnant mutants do not exhibit an increase in insulin content as seen in pregnant wild-type females (J:196854)
• 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 (J:196854)
• blood glucose is higher in pregnant mutant females at gestational day 19 than in wild-type pregnant females (J:196854)
• fasting blood glucose is increased in pregnant mutant females at gestational day 19 than in wild-type pregnant females (J:196854)
• plasma insulin levels are diminished in pregnant mutant females at gestational day 19 compared to wild-type pregnant females (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 (J:196854)
• 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 (J:196854)

cellular
• pregnant females show a decrease in beta-cell proliferation at gestational day 15, when maximal beta-cell proliferation normally occurs during pregnancy (J:196854)
• beta-cell proliferation is also decreased at postpartum day 4 (J:196854)
• however, beta-cell proliferation is similar to wild-type at gestational day 11 and 19 (J:196854)


Mouse Genome Informatics
cn10
    Mettm1Ics/Mettm1Sst
Tg(Nes-cre)1Kln/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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


Mouse Genome Informatics
cn11
    Mettm1Sst/Mettm1Sst
Tg(mI56i-cre,EGFP)1Kc/0

involves: 129P2/OlaHsd * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
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 (J:170554)
• open field activity and anxiety are not affected (J:170554)
• on reversal discriminations, mutants require more trials than controls, indicating impaired reversal learning
• mutants show increased latency performance on the cued-platform test, indicating a delay in striatal-dependent cued learning

nervous system
• 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)
• marker analysis indicates an increase in numbers of PV+ and SST+ striatal GABAergic interneurons
• however, striatum appears normal
• 31% reduction in PV+ cells in the orbitofrontal cortex
• 28% loss of PV+ cells in primary somatosensory cortex