Mouse Genome Informatics
hm1
    Ighmbp2nmd-2J/Ighmbp2nmd-2J
B6.BKS-Ighmbp2nmd-2J/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• at 62 days for males and 76 days for females
• maximum life span is 138 days for females

cardiovascular system
• degenerating and apoptotic
• nuclear blebbing
• secondary valvular insufficiency
• as early as 4-6 weeks of age
• pale, flaccid, enlarged hearts with one or more thrombi
• prolonged P-R interval
• attenuated, sometimes split
• prolonged and attenuated R waves
• decreased lower end systolic blood pressure

nervous system
• frequently show indications of secondary myelin degeneration
• sometimes lacking axons
• axon numbers in quadriceps nerves significantly decrease with age from 3 weeks on, 40% reduction by 12-14 weeks
• significant neuronal loss by 7 weeks in all lumbar ventral roots examined
• 56% of L4 motor axons lost
• numerous dystrophic axons in ventral roots
• most losses are of large axons
• 40% loss of small caliber axons
• vacuolation occurs during the course of myelination or after myelination
• abnormal cytoskeletons
• process of myelination normal
• denervation of motor endplates increases dramatically as motor neuron degeneration progresses

muscle
• degenerating and apoptotic
• nuclear blebbing
• as early as 4-6 weeks of age
• pale, flaccid, enlarged hearts with one or more thrombi
• and fatty infiltration
• severe muscle wasting and hind limb contracture
• centralized nuclei in myocytes
• development of diaphragmatic muscle degeneration occurs late, around 8-14 weeks
• severe diffuse myocyte degeneration and regeneration

behavior/neurological
• much shorter latency to fall when suspended from a wire cage top much shorter latence to fall when suspended from a wire cage top much shorter latence to fall when suspended from a wire cage top much shorter latence to fall when suspended from a wire cage top

respiratory system
• consolidation of lungs
• reduced breathing rate (bradypnea)

growth/size

homeostasis/metabolism
• 3-7 days prior to clearly evident clinical signs of heart disease, total plasma CK and cardiac-specific CK-MB levels in 5- to 9-week-old mice become significantly elevated
• consolidation of lungs
• and fatty infiltration


Mouse Genome Informatics
hm2
    Ighmbp2nmd-2J/Ighmbp2nmd-2J
BKS.Cg Dock7m +/+ Leprdb-Ighmbp2nmd-2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• death usually by 3.5 weeks although survival for several months is possible if left with parents without normal siblings present

behavior/neurological
• clench hindlimbs when picked up by the tail
• unable to grasp cage cover when set upon it
• rely on forelimbs to crawl forward, but balance and righting responses are normal
• dorsally contracted hindlimbs cannot be extended to stand erect or assume full posture on four limbs

muscle
• intermixture of very small muscle fibers with more normal fibers
• distal musculature of limbs more severely affected but focal areas of muscle degeneration proximally as well
• atrophic muscle fibers in the masseter
• atrophic muscle fibers in the temporalis muscle

nervous system
• affected alpha motor neurons with pale staining nuclei and perikarya
• mostly in lumbar region


Mouse Genome Informatics
cx3
    Ighmbp2nmd-2J/Ighmbp2nmd-2J
Tg(Eno2-Ighmbp2)17Cx/?

involves: C57BL/6J * C57BLKS/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• at 49 days for males and 54 days for females
• maximum life span is 87 days for females

cardiovascular system
• grossly dilated hearts with one or more thrombi
• prolonged P-R interval
• sometimes split

muscle
N
• grossly normal hind limb muscle phenotype (J:90418)
• grossly dilated hearts with one or more thrombi
• mild myopathic changes including myocyte degeneration and regeneration with centralized nucleii

nervous system
N
• axon morphology and nerve root diameters are normal (J:90418)

respiratory system
• consolidation of lungs
• reduced breathing rate (bradypnea)

growth/size

homeostasis/metabolism
• 3-7 days prior to clearly evident clinical signs of heart disease, total plasma CK and cardiac-specific CK-MB levels in 5- to 9-week-old mice become significantly elevated
• consolidation of lungs


Mouse Genome Informatics
cx4
    Ighmbp2nmd-2J/Ighmbp2nmd-2J
Tg(Ttn-Ighmbp2)45Cx/?

involves: C57BL/6J * C57BLKS/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• lifespan is longer than that of nmd-2J mutants but shorter than that of the wild-type controls and falls partway between the two points

nervous system
• severe skeletal muscle neurogenic atrophy

muscle
• resulting from the spinal motor neuron degeneration

behavior/neurological
• difficulty in mastication or deglutition

cardiovascular system
N
• mean ventricular free-wall thickness is normal (J:102748)

digestive/alimentary system
• difficulty in mastication or deglutition
• susceptible to mega-esophagus

growth/size
• the presence of the transgene does not rescue the weight loss found in nmd-2J homozygotes


Mouse Genome Informatics
cx5
    Ighmbp2nmd-2J/Ighmbp2nmd-2J
Tg(Ttn-Ighmbp2)108Cx/?

involves: C57BL/6J * C57BLKS/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• lifespan is longer than that of nmd-2J mutants but shorter than that of wild-type controls and falls partway between the two points

nervous system
• severe skeletal muscle neurogenic atrophy

muscle
• resulting from the spinal motor neuron degeneration

behavior/neurological
• difficulty in mastication or deglutition

cardiovascular system
N
• mean ventricular free-wall thickness is normal (J:102748)

digestive/alimentary system
• difficulty in mastication or deglutition
• susceptible to mega-esophagus

growth/size
• the presence of the transgene does not rescue the weight loss found in nmd-2J homozygotes


Mouse Genome Informatics
cx6
    Ighmbp2nmd-2J/Ighmbp2nmd-2J
Tg(Eno2-Ighmbp2)17Cx/?
Tg(Ttn-Ighmbp2)108Cx/?

involves: C57BL/6J * C57BLKS/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• increased heart weight proportionally distributed throughout all 4 chambers, but aside from this the presence of both transgenes rescues nmd-2J homozygotes to a wild-type phenotype including no cardiomyopathy


Mouse Genome Informatics
cx7
    Ighmbp2nmd-2J/Ighmbp2nmd-2J
Tg(Eno2-Ighmbp2)90Cx/?

involves: C57BL/6J * C57BLKS/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• phenotype is stated to be identical to that observed when Tg(Eno2-Ighmbp2)17Cx mice are used in this cross (GA Cox, personal communication)

growth/size

cardiovascular system

muscle
N
(J:90418)

respiratory system

nervous system

homeostasis/metabolism


Mouse Genome Informatics
cx8
    Ighmbp2nmd-2J/Ighmbp2nmd-2J
Tg(Eno2-Ighmbp2)17Cx/?
Tg(Ttn-Ighmbp2)45Cx/?

involves: C57BL/6J * C57BLKS/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• increased heart weight proportionally distributed throughout all 4 chambers, but aside from this the presence of both transgenes rescues nmd-2J homozygotes to a wild-type phenotype including no cardiomyopathy


Mouse Genome Informatics
cx9
    Ighmbp2nmd-2J/Ighmbp2nmd-2J
MnmC/MnmC

involves: C57BL/6J * C57BLKS/J * CAST/Ei * DBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: survival to as long as 7 months of age, but less as the B6 component of the background increases (J:51890)

cardiovascular system
• grossly dilated hearts with one or more thrombi
• prolonged P-R interval
• sometimes split

nervous system
• modest reduction in lumbar ventral root diameter
• 26% of L4 motor axons lost
• occasional dystrophic axons in ventral roots
• 25% loss of small caliber axons

behavior/neurological
• shorter latence to fall when suspended from a wire cage top

muscle
• grossly dilated hearts with one or more thrombi
• moderate myopathic changes
• milder muscle atrophy

respiratory system
• consolidation of lungs
• reduced breathing rate (bradypnea)

growth/size

homeostasis/metabolism
• 3-7 days prior to clearly evident clinical signs of heart disease, total plasma CK and cardiac-specific CK-MB levels in 5- to 9-week-old mice become significantly elevated
• consolidation of lungs


Mouse Genome Informatics
cx10
    Cmn1CAST/Ei/?
Ighmbp2nmd-2J/Ighmbp2nmd-2J
MnmC/MnmC

involves: C57BL/6J * C57BLKS/J * CAST/Ei * DBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• resistance to dilated cardiomyopathy
• increased survival time

muscle
• resistance to dilated cardiomyopathy
• increased survival time


Mouse Genome Informatics
cx11
    Cmn2CAST/Ei/?
Ighmbp2nmd-2J/Ighmbp2nmd-2J
MnmC/MnmC

involves: C57BL/6J * C57BLKS/J * CAST/Ei * DBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• resistance to dilated cardiomyopathy
• increased survival time

muscle
• resistance to dilated cardiomyopathy
• increased survival time


Mouse Genome Informatics
cx12
    Cmn3CAST/Ei/?
Ighmbp2nmd-2J/Ighmbp2nmd-2J
MnmC/MnmC

involves: C57BL/6J * C57BLKS/J * CAST/Ei * DBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• resistance to dilated cardiomyopathy in males
• increased survival time in males

muscle
• resistance to dilated cardiomyopathy in males
• increased survival time in males


Mouse Genome Informatics
cx13
    Cmn3C57BL/6J/?
Ighmbp2nmd-2J/Ighmbp2nmd-2J
MnmC/MnmC

involves: C57BL/6J * C57BLKS/J * CAST/Ei * DBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• resistance to dilated cardiomyopathy in females
• increased survival time in females

muscle
• resistance to dilated cardiomyopathy in females
• increased survival time in females