Mouse Genome Informatics
cn1
    Hand2tm1Dsr/Hand2tm2.1Dsr
Isl1tm1(cre)Tmj/Isl1+

involves: 129 * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cardiovascular system

cellular
• at E9.0, mice exhibit increased apoptosis in the pharyngeal mesoderm compared with wild-type mice


Mouse Genome Informatics
cn2
    Isl1tm1(cre)Tmj/Isl1+
Mapttm1(Ewsr1/Etv4)Arbr/Mapt+

involves: 129P2/OlaHsd * 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
• while sensory axons reach the skin only rudimentary sensory axon branching is established within the skin
• mice have 25% of the wild-type number of muscle spindles
• sensory afferents fail to invade the spinal cord and are found in an extreme lateral position at the dorsal root entry zone
• sensory afferents are bifurcated at the entry point
• sensory afferent fibers fail to approach the midline at the distal segments and continue to occupy an extreme lateral position
• unlike wild-type cells, dorsal root ganglia neurons survive in culture without the addition of neurotrophic agents
• whole dorsal root ganglia require neurotrophin-3 for survival

muscle
• mice have 25% of the wild-type number of muscle spindles


Mouse Genome Informatics
cn3
    Nrg1tm1Cbm/Nrg1tm3Cbm
Isl1tm1(cre)Tmj/Isl1+

involves: 129P2/OlaHsd * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• mutants exhibit a defect in muscle spindle differentiation in the dorsal root ganglion and motor neurons

nervous system
• mutants exhibit a defect in muscle spindle differentiation in the dorsal root ganglion and motor neurons
• selective absence of Schwann cells at E16.5 in adductor and gracilis muscles but not in other muscles
• parvalbumin+ proprioceptive afferents are present in E16.5 hindlimb muscles and initiate contact with individual myofibers, but they do not develop annulospiral branches around the myofibers
• parvalbumin+ proprioceptive terminals at muscle spindles remain primitive and unbranched at E18.5
• however, survival and initial differentiation of proprioceptive afferent sensory neurons is not impaired


Mouse Genome Informatics
cn4
    Maftm1.1Cbm/Maftm2.1Cbm
Isl1tm1(cre)Tmj/Isl1+

involves: 129P2/OlaHsd * 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
• large diameter axons in the saphenous nerve become thinner
• many myelinated axons greater than 4 um are lost in the interosseous nerve
• reduced in number and rudimentary
• however, NF200+ axons innervating the dermal papillae are normal
• reduced in number with axonal loss
• remaining corpuscles are small and have irregularly shaped cores
• innervating Pacinian corpuscles
• following skin indentation, mice exhibit prolonged rapid adapting mechanoreceptor (RAM) firing that continues into the beginning of the static phase with increased RAM spiking over a wide range of displacement amplitudes and shortened spike intervals compared with control mice
• following skin indentation, mice exhibit decreased von Frey thresholds of short adapting mechanoreceptors compared with control mice
• mice treated with linopirdine fail to exhibit a decrease in interspike interval in the saphenous nerve unlike control mice
• however, mice exhibit normal short adapting mechanoreceptor, D-hair receptors and Adelta nociceptor firing following skin indentation
• in large diameter but not medium diameter fibers

integument
• the hair in the dorsal hindpaw is shorter than the hair in the back skin and resembles hair of the tail

growth/size/body
• mild in adults
• however, mice exhibit normal body weight at P15

behavior/neurological
• on a rotarod test


Mouse Genome Informatics
cn5
    Smotm2Amc/Smotm2Amc
Isl1tm1(cre)Tmj/Isl1+

involves: 129S/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• embryos show severe inflow tract defects with pulmonary vein atresia
• embryos show severe inflow tract defects with pulmonary vein atresia
• embryos show persistence of aortopulmonary collateral circulation


Mouse Genome Informatics
cn6
    Isl1tm1(cre)Tmj/Isl1+
Shc1tm9Paw/Shc1tm9Paw

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mutants appear normal


Mouse Genome Informatics
cn7
    Isl1tm1(cre)Tmj/Isl1+
Shc1tm9Paw/Shc1tm9.1Paw

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mutants appear normal


Mouse Genome Informatics
cn8
    Brsk2tm2.1Jrs/Brsk2tm2.1Jrs
Isl1tm1(cre)Tmj/Isl1+

involves: 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
mortality/aging
• few mice survive beyond 24 hours after birth

nervous system
N
• interneurons exhibit normal migration to proper positions Golgi tendon organs are normally innervated (J:201695)
• reduced outgrowths from type Ia proprioceptive sensory neuron in dorsal root ganglia explants in the presence of NT-3 or NGF
• type Ia proprioceptive sensory neuron projections are disrupted and exhibit arrest at E15.5 as they reach the brainstem or ventral spinal cord in the medial spinal cord adjacent to the central canal and entire rostral-caudal extent of the spinal cord that persists through fetal development until P8 compared to in control mice
• type Ia proprioceptive sensory neuron projections fail to form terminal arbors
• mice exhibit defects in a second population of sensory neurons with few axons of the T12 dorsal root ganglion that cross the midline and only rare occurrences of axons that reach the proper contralateral target compared with control mice
• whisker axons have sparse arbors that fail to reach the correct target region in the bed nucleus of the stria terminalis (BSTC) without extensive branching
• however, mice exhibit normal growth of the sensory axons in the spinal cord and neuron targeting of nociceptive sensory axons in laminae I/IIi/IIo
• however, mice exhibit normal Pv+ proprioceptive axons growth into fore and hind limb muscles, trunk sensory axons form normal disc shaped endings on Merkel cells in the epidermis and axons in the deep vibrissal nerve that innervate whisker follicles
• type Ia proprioceptive sensory neuron projections are disrupted and exhibit arrest at E15.5 as they reach the brainstem or ventral spinal cord in the medial spinal cord adjacent to the central canal and entire rostral-caudal extent of the spinal cord that persists through fetal development until P8 compared to in control mice
• type Ia proprioceptive sensory neuron projections fail to form terminal arbors
• fewer proprioceptor axons in the cuneate nucleus, but not the cuneate fascicle
• however, growth of the sensory axons in the spinal cord is normal

behavior/neurological
• little milk in stomachs
• hypokinetic

cellular
• reduced outgrowths from type Ia proprioceptive sensory neuron in dorsal root ganglia explants in the presence of NT-3 or NGF


Mouse Genome Informatics
cn9
    Isl1tm1(cre)Tmj/Isl1+
Phox2btm3Jbr/Phox2btm3Jbr

involves: 129S2/SvPas * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• fails to form, on six sides out of eight, in four embryos
• missing, on five sides out of six, in three embryos


Mouse Genome Informatics
cn10
    Phox2btm3Jbr/Phox2btm3Jbr
Isl1tm1(cre)Tmj/Isl1+

involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 1 week after birth, few mice are still alive

nervous system
• mice exhibit abnormal development of facial neuron precursors that do not migrate into r6 unlike in wild-type mice
• mice exhibit impaired development of retrotapezoid nucleus neurons compared with wild-type mice
• the parafacial area e-pF oscillator exhibits only occasional motor activity bursts with reduced frequency compared to in wild-type mice
• rhythmic phrenic discharges are less frequent than in wild-type mice
• mice fail to exhibit an accelerated respiratory-like rhythm phrenic discharge in response to low pH challenge unlike similarly treated wild-type mice

growth/size/body
• surviving mice are smaller than wild-type mice

cellular
• mice exhibit abnormal development of facial neuron precursors that do not migrate into r6 unlike in wild-type mice
• mice exhibit impaired development of retrotapezoid nucleus neurons compared with wild-type mice


Mouse Genome Informatics
cn11
    Hand2tm1Dsr/Hand2tm2.1Dsr
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Isl1tm1(cre)Tmj/Isl1+

involves: 129S4/SvJaeSor * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• at E9.5, mice exhibit fewer progenitor cells migration into the outflow tract compared with control mice


Mouse Genome Informatics
cn12
    Stk11tm1.1Rdp/Stk11tm1.1Rdp
Isl1tm1(cre)Tmj/Isl1+

involves: 129S6/SvEvTac * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice are euthanized at 4 to 6 weeks due to massive gastrointestinal tumors
• however, mice survive to birth and postnatally

nervous system
N
• axon bundles are normal in the brainstem trigeminal complex, ascending tracts in the spinal cord (spinocerebellar, spinothalamic and dorsal funiculus), the optic nerve and motor and sensory nerves in the periphery (J:201695)
• mice exhibit normal type Ia proprioceptive sensory neuron projections to the ventral horn (J:201695)
• mice exhibit no sensory or motor deficit (J:201695)
• axons tracts in the cortical intermediate zone are reduced compared to in control mice
• thin-walled

tumorigenesis
• massive gastrointestinal tumors

behavior/neurological
N
• mice exhibit no sensory or motor deficit (J:201695)


Mouse Genome Informatics
cn13
    Aldh1a2tm1Soc/Aldh1a2tm2Soc
Isl1tm1(cre)Tmj/Isl1+

involves: 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E13.5 both ventral and dorsal projecting lateral motor column neurons appear stunted or atrophied and in some cases are retracted
• at E13.5 at the forelimb level the number of lateral motor column medial and lateral motor neurons are reduced by about 30% and 25%, respectively; however no difference in the number of lateral motor column lateral motor neurons is detected at E12.5
• at E13.5 at the hindlimb level the number of lateral motor column medial and lateral motor neurons are reduced by about 17% and 20%, respectively


Mouse Genome Informatics
cn14
    Etv1tm1Wds/Etv1tm1.1Wds
Isl1tm1(cre)Tmj/Isl1+

involves: 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• proprioceptive afferents terminate prematurely in the intrmediate zone of the spinal cord


Mouse Genome Informatics
cn15
    Gt(ROSA)26Sortm1(RARA*)Soc/Gt(ROSA)26Sortm1(RARA*)Soc
Isl1tm1(cre)Tmj/Isl1+

involves: 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice exhibit a 35% decrease in Lim1+/Islet2+ motor neurons compared to wild-type mice


Mouse Genome Informatics
cn16
    Isl1tm1(cre)Tmj/Isl1+
Tg(SOD1*G37R)1Dwc/0

involves: 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• overall survival is extended 64 days

nervous system
• in transgenic mice expressing a motorneuron specific Cre, disease onset is delayed 18 days
• progression from onset through early disease is delayed 31 days
• later disease progression is slowed with an average extension of 15 days

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:109131