Lrpap1<tm1Her> Targeted Allele Detail MGI Mouse (MGI:1857214)

Lrpap1^tm1Her
Targeted Allele Detail

Nomenclature

Symbol:	Lrpap1^tm1Her
Name:	low density lipoprotein receptor-related protein associated protein 1; targeted mutation 1, Joachim Herz
MGI ID:	MGI:1857214
Synonyms:	RAP-
Gene:	Lrpap1 Location: Chr5:35434139-35448415 bp, - strand Genetic Position: Chr5, 20.0 cM

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:43736
Parent Cell Line:	Other (see notes) (ES Cell)
Strain of Origin:	129S7/SvEvBrd

Mutation
description

Allele Type:	Targeted (knock-out)
Mutation:	Insertion
	A neomycin resistance cassette was inserted into sequences that encode the leader peptide. Immunoblot analysis of liver and brain did not detect the encoded protein in homozygous animals. (J:43736)

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 Lrpap1 Mutation:	3 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	cx3	cx4	tg5
behavior/neurological		√
abnormal spatial learning		√
		hm1	hm2	cx3	cx4	tg5
endocrine/exocrine glands		√
abnormal thyroid gland morphology		√
abnormal thyroid physiology		√
		hm1	hm2	cx3	cx4	tg5
homeostasis/metabolism			√		√
abnormal circulating protein level			√
abnormal lipid level					√
increased circulating cholesterol level					√
increased circulating triglyceride level					√
		hm1	hm2	cx3	cx4	tg5
nervous system		√				√
abnormal brain interneuron morphology		√
astrocytosis						√
amyloid beta deposits						√
		hm1	hm2	cx3	cx4	tg5
other phenotype			√			√
other aberrant phenotype			√
amyloid beta deposits						√
		hm1	hm2	cx3	cx4	tg5
renal/urinary system		√
abnormal kidney physiology		√
		hm1	hm2	cx3	cx4	tg5
normal phenotype				N
no abnormal phenotype detected				N

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Lrpap1^tm1Her/Lrpap1^tm1Her	B6.129S7-Lrpap1^tm1Her
renal/urinary system abnormal kidney physiology (J:106203) endocytotic machinery in the proximal tubule is disturbed athough the ability to adjust to dietary phosphate levels is unaffected endocrine/exocrine glands abnormal thyroid gland morphology (J:107358) slight thyrocyte and nuclear hypertrophy but no goiter abnormal thyroid physiology (J:107358) slightly reduced thyroglobulin in thyroid follicles but intracellular levels and levels on the apical membrane of thyrocytes are increased T4 levels in thyroglobulin are normal or slightly elevated free T4 levels unchanged TSH levels are elevated but not to the point of statistical significance nervous system abnormal brain interneuron morphology (J:107552) levels of somatostatin in neurons reduced number of neurons expressing somatostatin is reduced behavior/neurological abnormal spatial learning (J:107552) poorer performance in a Morris water maze after 6 days of training, swim a greater distance to find target than do controls
Genotype	Allelic Composition	Genetic Background
hm2	Lrpap1^tm1Her/Lrpap1^tm1Her	involves: 129S7/SvEvBrd * C57BL/6J
homeostasis/metabolism abnormal circulating protein level (J:43736) alpha2 macroglobulin is removed from the circulation at about 25% of the normal rate no effect is seen on blood lipoproteins regardless of diet homozygotes thrived well and are superficially normal other phenotype other aberrant phenotype (J:43736) reduces expression of lipoprotein receptor related protein by 75% but has no effect on the LDL receptor
Genotype	Allelic Composition	Genetic Background
cx3	Lrp1b^tm1Her/Lrp1b^tm1Her Lrpap1^tm1Her/Lrpap1^tm1Her	involves: 129S/SvEv * C57BL/6
normal phenotype no abnormal phenotype detected (J:90197) homozygous mutants appear normal and have normal brain physiology
Genotype	Allelic Composition	Genetic Background
cx4	Ldlr^tm1Her/Ldlr^tm1Her Lrpap1^tm1Her/Lrpap1^tm1Her	involves: 129S7/SvEvBrd * C57BL/6J
homeostasis/metabolism abnormal lipid level (J:43736) chylomicron reminent and LDL levels increased in blood increased circulating cholesterol level (J:43736) 2 fold increase in total plasma cholesterol increased circulating triglyceride level (J:43736) moderately increased plasma triglyceride levels
Genotype	Allelic Composition	Genetic Background
tg5	Lrpap1^tm1Her/Lrpap1^tm1Her Tg(APPV717F)109Ili/0	involves: 129S7/SvEvBrd * C57BL/6 * DBA/2
nervous system astrocytosis (J:107567) develop reactive astrocytosis amyloid beta deposits (J:107567) elevated amyloid deposits over controls other phenotype amyloid beta deposits (J:107567) elevated amyloid deposits over controls

Notes

ES cell line = AB1 (129S7/SvEvBrd-Hprt1⁺) or JH1 (129S7/SvEvBrd).

References

Original:	J:43736 Willnow TE et al., "Functional expression of low density lipoprotein receptor-related protein is controlled by receptor-associated protein in vivo." Proc Natl Acad Sci U S A 1995 May 9;92(10):4537-41
All:	13 reference(s)

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