Alox5<tm1Fun> Targeted Allele Detail MGI Mouse (MGI:1857125)

Alox5^tm1Fun
Targeted Allele Detail

Nomenclature

Symbol:	Alox5^tm1Fun
Name:	arachidonate 5-lipoxygenase; targeted mutation 1, Colin Funk
MGI ID:	MGI:1857125
Synonyms:	5-LO KO, 5-LO^-, 5-LOX K/O, 5-LOX^-, 5LX-
Gene:	Alox5 Location: Chr6:116360089-116411196 bp, - strand Genetic Position: Chr6, 53.2 cM

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:21372
Parent Cell Line:	D3H (ES Cell)
Strain of Origin:	129S2/SvPas

Mutation
description

Allele Type:	Targeted (knock-out)
Mutation:	Insertion
	Insertion of a neomycin resistance cassette into exon 6 disrupted the Alox5 gene. RT-PCR studies did not detect transcript in resident peritoneal macrophages of homozygous mutant mice. Western blot analysis of resident peritoneal macrophages of homozygous mutant mice did not detect ALOX5. (J:21372)

Find Mice (IMSR)

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

Carrying this Mutation:	Mouse Strains: 3 strains available Cell Lines: 0 lines available
Carrying any Alox5 Mutation:	4 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	hm2	hm3
adipose tissue		√
increased total fat pad weight		√
		hm1	hm2	hm3
cardiovascular system				N
cardiovascular system phenotype				N
		hm1	hm2	hm3
hematopoietic system				√
hematopoietic system phenotype				N
small spleen				√
		hm1	hm2	hm3
homeostasis/metabolism		√
increased circulating leptin level		√
increased circulating VLDL cholesterol level		√
		hm1	hm2	hm3
immune system		√	N	√
immune system phenotype			N	N
small spleen				√
abnormal immune system physiology				√
decreased susceptibility to autoimmune disorder		√
decreased inflammatory response				√
		hm1	hm2	hm3
skeleton		√
increased bone density		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Alox5^tm1Fun/Alox5^tm1Fun	B6.129S2-Alox5^tm1Fun/J
adipose tissue increased total fat pad weight (J:104825) increased total fat pad weight homeostasis/metabolism increased circulating leptin level (J:104825) increased circulating VLDL cholesterol level (J:104825) increased plasma VLDL/LDL cholesterol skeleton increased bone density (J:104825) increased bone mineral density immune system decreased susceptibility to autoimmune disorder (J:108446) upon adoptive transfer of IRBP1-20-specific T cells from wild-type B6 donors to wild-type and Alox5-deficient recipients, wild-type mice develop severe clinical uveitis, whereas mutant recipients show only mild and transient clinical disease
Genotype	Allelic Composition	Genetic Background
hm2	Alox5^tm1Fun/Alox5^tm1Fun	B6.Cg-Alox5^tm1Fun
immune system immune system phenotype (J:89268) homozygotes display no differences in infarct size following induction of focal cerebral ischemia (permanent or transient; 60 min) relative to wild-type
Genotype	Allelic Composition	Genetic Background
hm3	Alox5^tm1Fun/Alox5^tm1Fun	involves: 129S2/SvPas * C57BL/6
cardiovascular system cardiovascular system phenotype (J:21372) homozygotes display a normal mean arterial pressure and heart rate relative to wild-type hematopoietic system hematopoietic system phenotype (J:21372) analysis of cell-surface markers CD3, CD4 and B220 on splenocytes from 4-wk- and 8-wk-old mice revealed no other abnormalities homozygotes show no changes in total blood cell populations or differential cell counts bone marrow analysis revealed no evidence of abnormal precursor cells of any lineage relative to wild-type small spleen (J:21372) homozygotes show no abnormalities up to 10 months of age under normal physiological conditions; however, their spleen is usually smaller relative to wild-type immune system immune system phenotype (J:21372) homozygotes display a normal reaction to endotoxin-induced shock also, homozygotes exhibit a normal reaction to ear inflammation induced by topical application of phorbol myristyl acetate neutrophil recruitment into the peritoneal cavity by a non-specific inflammatory challenge (glycogen) elicits a comparable (large) influx of polymorphonuclear leukocytes in both wild-type and mutant mice small spleen (J:21372) homozygotes show no abnormalities up to 10 months of age under normal physiological conditions; however, their spleen is usually smaller relative to wild-type abnormal immune system physiology (J:21372) conscious, unanaesthetized homozygotes show resistance to the lethal effects of platelet-activating factor (PAF): they display the same listless behavior as wild-type for the first 20 min but recover quickly mechanically ventilated, anesthetized homozygotes show no signs of broncho-constriction; however, broncho-constriction is observed after methacholine challenge decreased inflammatory response (J:21372, J:75371) homozygotes show a significantly reduced reaction to arachidonic acid-induced ear inflammation; administration of leukotrienes rescues this inflammatory phenotype: inflammation is rapid in onset and maximal swelling is reached between 30-60 min (J:21372) homozygotes display a significantly reduced chemotactic infiltration by polymorphonuclear leukocytes following induction of immune complex peritonitis (reverse passive Arthus reaction) (J:21372) in the thioglycollate-elicited peritonitis model, homozygotes only generate about 50% as much peritoneal leukocytosis as wild-type mice at 4.5 h after i.p. thioglycollate challenge; as expected, leukotriene B4 is absent from the mutant peritoneal fluid (J:75371) the specific arachidonate 5-lipoxygenase inhibitor, zileuton, has no effect on the peripheral white-cell count in mutant mice (J:75371)

References

Original:	J:21372 Chen XS et al., "Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene." Nature 1994 Nov 10;372(6502):179-82
All:	45 reference(s)

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