Mouse Genome Informatics
ht1
    Mnx1tm4(cre)Tmj/Mnx1+
involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• compared with Gt(ROSA)26Sortm1(CAG-PLS3,-GFP)Bwir heterozygotes

nervous system
• mice exhibit reduced endplate size compared with Gt(ROSA)26Sortm1(CAG-PLS3,-GFP)Bwir heterozygotes


Mouse Genome Informatics
cn2
    Mnx1tm4(cre)Tmj/Mnx1+
Smn1tm1Cdid/Smn1tm1Cdid
Tg(SMN2)89Ahmb/0

involves: 129 * 129S1/Sv * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival of 12 days

nervous system
N
• neuromuscular junctions are similar to controls in the intercostal and triangularis sterni muscles (J:183080)
• decrease in cardiac autonomic innervation
• in L3-L5 spinal cord sections but not in the cervical or thoracic regions

cardiovascular system
• end-stage mice display skipped or dropped beats
• at P9-P11
• at P9-P11

behavior/neurological
N
• ambulatory throughout life (J:183080)
• lateral instability of the hind limbs
• significantly improved righting response
• early in life
• outgrow this passive behavior after P6

growth/size

Mouse Models of Human Disease
OMIM IDRef(s)
Spinal Muscular Atrophy, Type I; SMA1 253300 J:183080


Mouse Genome Informatics
cn3
    Mapttm1(Ewsr1/Etv4)Arbr/Mapt+
Mnx1tm4(cre)Tmj/Mnx1+

involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice have very few dorsal root ganglia neurons at brachial levels and increasingly more neurons progressing caudally undergo recombination

cellular
• mice have very few dorsal root ganglia neurons at brachial levels and increasingly more neurons progressing caudally undergo recombination


Mouse Genome Informatics
cn4
    Lrp4tm1.1Line/Lrp4tm1.1Line
Mnx1tm4(cre)Tmj/Mnx1+
Tg(ACTA1-cre)79Jme/0

involves: 129S/SvEv * 129S1/Sv * C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• with cyanosis

nervous system
• increased number and length of secondary or intramuscular branches with tertiary and quaternary branches
• secondary branches are longer than in Lrp4tm1.1Line/Lrp4tm1.1Line Tg(ACTA1-cre)79Jme mice
• nerve terminals are fragmented in diaphragm
• severely impaired formation
• almost undetectable in the diaphragm at E13.5
• fewer and smaller AChR clusters

homeostasis/metabolism
• soon after birth


Mouse Genome Informatics
cn5
    Lrp4tm1.1Line/Lrp4tm1.1Line
Mnx1tm4(cre)Tmj/Mnx1+

involves: 129S/SvEv * 129S1/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• mice exhibit normal neuromuscular synapse formation (J:188352)


Mouse Genome Informatics
cn6
    Fgd4tm1Ics/Fgd4tm1Ics
Mnx1tm4(cre)Tmj/Mnx1+

involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• normal myelination of plantaris, quadriceps or saphenous nerves (J:190437)


Mouse Genome Informatics
cn7
    Gt(ROSA)26Sortm1(CAG-PLS3,-GFP)Bwir/Gt(ROSA)26Sor+
Mnx1tm4(cre)Tmj/Mnx1+

involves: 129S1/Sv * 129S4/SvJae * BALB/cJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
N
• mice exhibit normalized muscle fiber size compared with Mnx1tm4(cre)Tmj heterozygotes (J:193844)

nervous system
N
• mice exhibit normalized endplate size compared with Mnx1tm4(cre)Tmj heterozygotes (J:193844)


Mouse Genome Informatics
cn8
    Gfra1tm2Jmi/Gfra1tm2Jmi
Mnx1tm4(cre)Tmj/Mnx1+

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• loss of small diameter but not large diameter axons in lumbar ventral roots and in distal medial gastrocnemius nerve


Mouse Genome Informatics
cn9
    Dlg1tm1Rlh/Dlg1tm1Rlh
Mnx1tm4(cre)Tmj/Mnx1+

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice exhibit an 80% decrease in dendrite branches, a 50% reduction in overall tree size, a 50% reduction in average dendrite length and a 15% reduction in the length of the longest dendrite compared to in wild-type mice


Mouse Genome Informatics
cn10
    Mnx1tm4(cre)Tmj/Mnx1+
Mycbp2tm1Adia/Mycbp2tm1Adia

involves: 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some mice are stillborn while others survive into adulthood and are fertile

nervous system
• mice exhibit neurofilament-rich sprouts that extend beyond normally innervated endplates

respiratory system
N
• diaphragms exhibit full innervation unlike in Phr1tm1.1Adia homozygotes (J:125702)


Mouse Genome Informatics
cn11
    Mnx1tm4(cre)Tmj/Mnx1+
Rettm2(RET)Heno/Rettm2(RET)Heno

involves: 129S1/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• fusimotor axons are unaffected (J:132854)


Mouse Genome Informatics
cn12
    Mnx1tm4(cre)Tmj/Mnx1+
Tardbptm1.1Ckjs/Tardbptm1.2Cjks

involves: 129S1/Sv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• average lifespan of mutants showing amyotrophic lateral sclerosis-like phenotypes is 10 months

growth/size
• average weight is slightly lower at early birth than in controls and this difference becomes more pronounced with age, with a significant weight difference after 8 weeks of age
• while mutants show a peak of weight gain during 90-100 days of age, soon after this time, they begin to show weight loss

behavior/neurological
• abnormal hind limb clasping is seen after 13 weeks of age
• mutants show a deficiency in the rotarod test after 13 weeks of age

immune system
• microglia activation is seen in the lateroventral lumbar spinal cord

muscle
• more males than females develop amyotrophic lateral sclerosis-like phenotypes with a male/female ratio of 3:1

nervous system
• microglia activation is seen in the lateroventral lumbar spinal cord
• in the spinal cord
• accumulation of ubiquitinated proteins in the spinal cord motor neurons at 20 weeks of age
• progressive loss of motor neurons, with a 10% decrease of spinal cord motor neurons at 10 weeks of age and a large loss of ChAT-positive motor neurons at 20 weeks of age
• 46% and 25% reduction in alpha and gamma motor neurons, respectively, in the lumbar regions of the spinal cord at 20 weeks of age
• more males than females develop amyotrophic lateral sclerosis-like phenotypes with a male/female ratio of 3:1
• motor neuron loss, reactive astrocytosis, microglia activation and accumulation of polyubiquitinated proteins in the ventral horn

skeleton
• mutants exhibit kyphosis beginning at 20 weeks of age which becomes severe at 24 weeks

hematopoietic system
• microglia activation is seen in the lateroventral lumbar spinal cord

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:190254


Mouse Genome Informatics
cn13
    Mnx1tm4(cre)Tmj/Mnx1+
Isl2tm1Arbr/Isl2+

involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice lack motor neurons when examined from E12 to E16.9 (J:69623)


Mouse Genome Informatics
cn14
    Mnx1tm4(cre)Tmj/Mnx1+
Rettm2(RET)Heno/Rettm2(RET)Heno

involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• absence of fusimotor nerve terminals
• loss of small diameter but not large diameter axons in lumbar ventral roots and in distal medial gastrocnemius nerve