Sod2<tm1Leb> Targeted Allele Detail MGI Mouse (MGI:1857480)

Sod2^tm1Leb
Targeted Allele Detail

Nomenclature

Symbol:	Sod2^tm1Leb
Name:	superoxide dismutase 2, mitochondrial; targeted mutation 1, Russell M Lebovitz
MGI ID:	MGI:1857480
Synonyms:	Sod2^-, SOD2^m1BCM, Sod2^mlbcm
Gene:	Sod2 Location: Chr17:13200848-13208219 bp, + strand Genetic Position: Chr17, 7.6 cM

Histological abnormalities in Sod2^tm1Leb/Sod2^tm1Leb mice

Show the 2 image(s) involving this allele.

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:36148
Parent Cell Line:	AB2.1 (ES Cell)
Strain of Origin:	129S7/SvEvBrd-Hprt1^b-m2

Mutation
description

Allele Type:	Targeted (knock-out)
Mutations:	Insertion, Intragenic deletion
	A human HPRT minigene driven by the PGK promoter replaced exons 1 and 2, and sequences approximately 500 bp immediately 5' of exon 1. The replaced region encodes the transcription and translation start sites, the mitochondrial targeting sequence, and one of three histidines that bind directly to the manganese cofactor. Northern blot analysis of brain did not detect mRNA in homozygous mutant mice. Enzyme activity assays of heart did not detect active protein in homozygous mutant mice. (J:36148)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 2 strains available Cell Lines: 0 lines available
Carrying any Sod2 Mutation:	6 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	ht2
adipose tissue		√
decreased adipose tissue amount		√
		hm1	ht2
behavior/neurological		√
abnormal motor capabilities/coordination/movement		√
circling		√
weakness		√
fatigue		√
		hm1	ht2
cardiovascular system		√
thin ventricular wall		√
dilated cardiomyopathy		√
		hm1	ht2
cellular		√
abnormal mitochondrial physiology		√
		hm1	ht2
growth/size		√
decreased body size		√
decreased body length		√
decreased body weight		√
postnatal growth retardation		√
		hm1	ht2
hearing/vestibular/ear		√	N
hearing/vestibular/ear phenotype			N
circling		√
		hm1	ht2
hematopoietic system		√
anemia		√
impaired myelopoiesis		√
decreased bone marrow cell number		√
		hm1	ht2
homeostasis/metabolism		√
abnormal lipid homeostasis		√
		hm1	ht2
immune system		√
impaired myelopoiesis		√
		hm1	ht2
lethality/postnatal		√
postnatal lethality		√
		hm1	ht2
liver/biliary system		√
abnormal hepatocyte morphology		√
		hm1	ht2
muscle		√
dilated cardiomyopathy		√
decreased skeletal muscle mass		√
		hm1	ht2
nervous system		√
neurodegeneration		√
		hm1	ht2
reproductive system		N
reproductive system phenotype		N
		hm1	ht2
skin/coat/nails		√
pallor		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Sod2^tm1Leb/Sod2^tm1Leb	B6.129S7-Sod2^tm1Leb/J
Histological abnormalities in Sod2^tm1Leb/Sod2^tm1Leb mice lethality/postnatal postnatal lethality (J:36148) homozygotes survive for up to 3 weeks of age mutants with the slowest growth rates (4 of 8) usually die during the first postnatal week mutants with intermediate growth rates die within the second or third week growth/size decreased body size (J:36148) at P10, homozygotes are significantly smaller than wild-type littermates however, no skeletal abnormalities are observed and failure to thrive is unrelated to nursing difficulties decreased body length (J:36148) decreased body weight (J:36148) postnatal growth retardation (J:36148) reduction of postnatal growth rate is variable among mice, first evident between P2 and P7, and progressive until death by P18 behavior/neurological abnormal motor capabilities/coordination/movement (J:36148) homozygotes display striking and progressive motor deficits circling (J:36148) weakness (J:36148) homozygotes exhibit progressive limb weakness, as shown by impaired ability to hold onto a bar suspended above the cage for at least 5 sec without falling or scale a 60 degree incline fatigue (J:36148) homozygotes display earlier onset of fatigue, as shown by reduced endurance only after 2-3 cycles of immersion into a small room-temperature water bath (vs 10 cycles in wild-type mice) hematopoietic system anemia (J:36148) homozygotes are severely anemic at the time of death impaired myelopoiesis (J:36148) within the bone marrow, all hematopoietic lineages appear to be reduced decreased bone marrow cell number (J:36148) homozygotes display a hypocellular bone marrow nervous system neurodegeneration (J:36148) homozygotes display degeneration of large CNS neurons, esp. in the basal ganglia and brainstem neurodegeneration is associated with extensive mitochondrial damage, loss of polysomes, clearing of the cytoplasm, a relative absence of rough ER, focal dilation of smooth ER, and ruffling of nuclear membranes in P10 basal ganglia, early cellular degeneration includes dispersion of cytoplasm, shedding of ribosomes, and balloning of mitochondria in affected brain and brainstem regions, occasional swollen neurites are observed; however, most structures and mitochondria remain intact cellular abnormal mitochondrial physiology (J:36148) at >P7, homozygotes show extensive mitochondrial injury in affected cardiac muscle cells and degenerating neurons adipose tissue decreased adipose tissue amount (J:36148) homozygotes display a significant reduction in adipose tissue mass muscle dilated cardiomyopathy (J:36148) only 10% of homozygotes display extreme baloon-like cardiac dilatation with thinning of the ventricular wall affected myocytes exhibit widespread cellular injury and death associated with mitochondrial injury (swelling and fragmentation) and lipid peroxidation of mitochondrial membranes in severely affected resgions decreased skeletal muscle mass (J:36148) homozygotes display a significant reduction in skeletal muscle mass immune system impaired myelopoiesis (J:36148) within the bone marrow, all hematopoietic lineages appear to be reduced liver/biliary system abnormal hepatocyte morphology (J:36148) hepatic glycogen deposits appear coarsely granular and with a tendency towards centrilobular accumulation in addition, an abundance of intracellular lipid vacuoles is observed cardiovascular system thin ventricular wall (J:36148) homozygotes with extreme baloon-like cardiac dilatation (10%) display thinning of the ventricular wall dilated cardiomyopathy (J:36148) only 10% of homozygotes display extreme baloon-like cardiac dilatation with thinning of the ventricular wall affected myocytes exhibit widespread cellular injury and death associated with mitochondrial injury (swelling and fragmentation) and lipid peroxidation of mitochondrial membranes in severely affected resgions homeostasis/metabolism abnormal lipid homeostasis (J:36148) homozygotes display an abundance of intracellular lipid vacuoles in hepatocytes homozygotes with extreme cardiac dilatation exhibit lipid peroxidation of mitochondrial membranes in affected myocytes homozygotes without extreme cardiac dilatation show increased accumulation of neutral lipid in myocytes but no mitochondrial injury hearing/vestibular/ear circling (J:36148) skin/coat/nails pallor (J:36148) homozygotes appear slightly pale reproductive system reproductive system phenotype (J:64299) ovaries from female homozygotes (4-10 days of age), transplanted to the bursa of wild-type hosts, display all stages of folliculogenesis including corpora lutea and give rise to viable offspring, suggesting normal ovarian function
Genotype	Allelic Composition	Genetic Background
ht2	Sod2^tm1Leb/Sod2⁺	B6.129S7-Sod2^tm1Leb/J
hearing/vestibular/ear hearing/vestibular/ear phenotype (J:119972) aging heterozygotes exhibit no significant increase in the amount of age-related hearing loss relative to C57BL/6 control mice, with many animals over the age of 20 months being deaf or displaying ABR thresholds >80 dB SPL contrary to expectation, ABR thresholds are only 12 dB higher in heterozygotes relative to C57BL/6 control mice (at various age groups including 6-9, 12, 15, 18-21 and 24 months and stimuli including click, 8, 16 and 32 kHz); no explanation for the relatively good hearing of three 24-month-old heterozygotes is provided

References

Original:	J:36148 Lebovitz RM et al., "Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice." Proc Natl Acad Sci U S A 1996 Sep 3;93(18):9782-7
All:	23 reference(s)

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