Bace1<tm1Pcw> Targeted Allele Detail MGI Mouse (MGI:2389228)

Bace1^tm1Pcw
Targeted Allele Detail

Nomenclature

Symbol:	Bace1^tm1Pcw
Name:	beta-site APP cleaving enzyme 1; targeted mutation 1, Philip C Wong
MGI ID:	MGI:2389228
Synonyms:	BACE1^-
Gene:	Bace1 Location: Chr9:45646666-45670524 bp, + strand Genetic Position: Chr9, Syntenic

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:79847
Parent Cell Line:	R1 (ES Cell)
Strain of Origin:	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺

Mutation
description

Allele Type:	Targeted (knock-out)
Mutations:	Insertion, Intragenic deletion
	Exon 1 was replaced with a neomycin selection cassette inserted by homologous recombination. Normal protein was undetected by Western blot analysis of homozygous mutant embryos. (J:79847)

Find Mice (IMSR)

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

Carrying this Mutation:	Mouse Strains: 1 strain available Cell Lines: 0 lines available
Carrying any Bace1 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	tg3	tg4
behavior/neurological		√	√	√	√
behavior/neurological phenotype				N
abnormal grip strength		√
decreased thermal nociceptive threshold		√
decreased anxiety-related response			√	√
abnormal spatial learning			√		√
abnormal spatial reference memory			√		√
abnormal spatial working memory			√
abnormal locomotor activation			√	√
		hm1	hm2	tg3	tg4
nervous system		√	√		√
abnormal myelin sheath morphology		√
abnormal myelination		√
enhanced paired-pulse facilitation			√
abnormal long term depression			√
amyloid beta deposits					√
		hm1	hm2	tg3	tg4
other phenotype				N	√
other phenotype phenotype				N
amyloidosis					√
amyloid beta deposits					√
		hm1	hm2	tg3	tg4
touch/vibrissae		√
decreased thermal nociceptive threshold		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Bace1^tm1Pcw/Bace1^tm1Pcw	involves: 129S1/Sv * 129X1/SvJ
behavior/neurological abnormal grip strength (J:116162) mice show reduced grip strength (1.13) relative to wild-type controls (1.26) decreased thermal nociceptive threshold (J:116162) mutants retract paws from thermal stimulus more rapidly than wild-type controls, indicating greater pain sensitivity nervous system abnormal myelin sheath morphology (J:116162) in 2-month old mice, myelin sheaths are significantly thinner in optic nerves compared to wild-type controls more axons in sciatic nerve of mutants appear smaller in diameter than in wild-type abnormal myelination (J:116162) hypomyelination is observed in hippocampus and cerebral cortex at P15 and P30, but axonal development is normal sciatic nerve is hypomyelinated in mutants touch/vibrissae decreased thermal nociceptive threshold (J:116162) mutants retract paws from thermal stimulus more rapidly than wild-type controls, indicating greater pain sensitivity
Genotype	Allelic Composition	Genetic Background
hm2	Bace1^tm1Pcw/Bace1^tm1Pcw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
behavior/neurological decreased anxiety-related response (J:123534) in an open-field task, mice display low anxiety-type behavior like greater distance traveled and more frequent and active visits to open center of field compared to control heterozygotes and wild-type mice abnormal spatial learning (J:123534) abnormal spatial reference memory (J:123534) in Morris water maze, 3-month old mice show normal learning and memory for location of hidden platform, but at 16 months, mutant animals display significantly impaired spatial reference memory during probe trials compared to normal or heterozygous littermates, while performance in hidden platform trials is not significantly different abnormal spatial working memory (J:123534) in spatial working memory tasks using the radial arm water maze, mice are significantly impaired compared to littermates; deficit is observed in Y-maze task, with mutant animals showing deficits in arm alternation abnormal locomotor activation (J:123534) swimming speed is lower than controls in Morris water maze nervous system enhanced paired-pulse facilitation (J:123534) the PPF ratio is significantly increased at short interstimulus intervals (ISIs) relative to controls, but not at long ISIs abnormal long term depression (J:123534) after LTD saturation, mice display a larger de-depression than controls
Genotype	Allelic Composition	Genetic Background
tg3	Bace1^tm1Pcw/Bace1^tm1Pcw Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J
behavior/neurological behavior/neurological phenotype (J:123534) mice perform as well as control mice in platform and probe trials in Morris water maze tasks decreased anxiety-related response (J:123534) in open field test, mice are similar to Bace1^tm1Pcw homozygotes, and spend more time in open area at center of field than at periphery abnormal locomotor activation (J:123534) swim speed is lower than other genotypes and nontransgenic mice in hidden and visible platform trials other phenotype other phenotype (J:123534) in 12- or 20-month old mice, no amyloid beta (Abeta) aggregation is detected in brains; no amyloid deposits are found
Genotype	Allelic Composition	Genetic Background
tg4	Bace1^tm1Pcw/Bace1⁺ Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J
behavior/neurological abnormal spatial learning (J:123534) abnormal spatial reference memory (J:123534) mice are significantly impaired in Morris water maze tasks nervous system amyloid beta deposits (J:123534) high level of amyloid beta aggregates are found in brain at 12 months of age other phenotype amyloidosis (J:123534) in 12-month old brains, there is a 27% reduction in amyloid beta aggregates compared to transgenic mice that are wild-type for Bace1; there are no significant differences at 20 months in 12-month old brains, there is 37% reduction in percentage of brain volume occupied by amyloid beta deposits, but no difference at 20 months amyloid beta deposits (J:123534) high level of amyloid beta aggregates are found in brain at 12 months of age

References

Original:	J:79847 Cai H et al., "BACE1 is the major beta-secretase for generation of Abeta peptides by neurons." Nat Neurosci 2001 Mar;4(3):233-4
All:	10 reference(s)

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