Sirt1<tm1Mcby> Targeted Allele Detail MGI Mouse (MGI:2448246)

Sirt1^tm1Mcby
Targeted Allele Detail

Summary

Symbol:	Sirt1^tm1Mcby
Name:	sirtuin 1; targeted mutation 1, Michael W McBurney
MGI ID:	MGI:2448246
Synonyms:	Sir2-, sir2alpha null, SIRT1^-, Sirt1 KO
Gene:	Sirt1 Location: Chr10:63154784-63174814 bp, - strand Genetic Position: Chr10, 32.57 cM
Alliance:	Sirt1^tm1Mcby page

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:81010
Parent Cell Line:	R1 (ES Cell)
Strain of Origin:	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺

Mutation
description

Allele Type:		Targeted (Null/knockout)
Mutations:		Insertion, Intragenic deletion
		Mutation details: The gene was disrupted by replacement of exons 5 and 6, which encode a large portion of the catalytic domain, with a hygromycin resistance cassette via homologous recombination. Northern blot analysis of RNA from homozygous mutant E12.5 embryos and adult tissues did not detect gene expression. (J:81010)

Phenotypes

Key:

hm	homozygous	ht	heterozygous	tg	involves transgenes	√	phenotype observed
cn	conditional genotype	cx	complex: > 1 genome feature	ot	other: hemizygous, indeterminate,...	N	normal phenotype

Genotype/
Background:

	Allelic Composition	Genetic Background	Cell Line(s)

	Allelic Composition	Genetic Background
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hm1	Sirt1^tm1Mcby/Sirt1^tm1Mcby	129/Sv-Sirt1^tm1Mcby
hm2	Sirt1^tm1Mcby/Sirt1^tm1Mcby	involves: 129
hm3	Sirt1^tm1Mcby/Sirt1^tm1Mcby	involves: 129S1/Sv * 129X1/SvJ
hm4 Disease Model	Sirt1^tm1Mcby/Sirt1^tm1Mcby	involves: 129S1/Sv * 129X1/SvJ * CD-1
cx5	Actb^{tm3.1(Sirt1)Npa}/Actb⁺ Sirt1^tm1Mcby/Sirt1^tm1Mcby	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J

Phenotypes:

Affected Systems	hm1		hm2	hm3		hm4		cx5
show or hide all annotated terms Sex:
adipose tissue						√	√
abnormal inguinal fat pad morphology						√	√
behavior/neurological				√	√	√	√
lethargy				√	√
polydipsia						√	√
polyphagia						√	√
decreased locomotor activity						√	√
abnormal nursing						√
cardiovascular system			√			√	√
heart right ventricle hypertrophy			√			√	√
cellular		√				√	√
oligozoospermia							√
teratozoospermia							√
abnormal sperm flagellum morphology							√
globozoospermia							√
abnormal spermatid morphology							√
decreased spermatid number		√
abnormal spermatocyte morphology		√
multinucleated giant male germ cells		√
arrest of male meiosis		√
increased male germ cell apoptosis		√					√
immotile sperm							√
abnormal cellular respiration						√	√
craniofacial			√	√	√	√	√
abnormal palatal rugae morphology				√	√
short snout			√	√	√	√	√
digestive/alimentary system			√	√	√	√	√
abnormal palatal rugae morphology				√	√
exocrine pancreas atrophy			√			√	√
abnormal salivary gland morphology				√	√
embryo			√			√	√
decreased embryo size			√			√	√
endocrine/exocrine glands		√	√	√	√	√	√
exocrine pancreas atrophy			√			√	√
abnormal salivary gland morphology				√	√
abnormal lacrimal gland morphology				√	√
absent corpus luteum						√
small ovary						√
abnormal seminiferous tubule morphology		√
abnormal seminiferous tubule epithelium morphology							√
small seminiferous tubules		√
abnormal Sertoli cell development		√
abnormal adult Leydig cell differentiation		√
decreased Leydig cell number		√
decreased testis weight							√
increased insulin secretion						√	√
decreased testes secretion		√
growth/size/body		√	√	√	√	√	√	N
growth/size/body region phenotype								N
heart right ventricle hypertrophy			√			√	√
abnormal palatal rugae morphology				√	√
short snout			√	√	√	√	√
decreased embryo size			√			√	√
decreased body size		√		√	√
decreased body weight			√	√	√	√	√
slow postnatal weight gain						√	√
postnatal growth retardation		√
hematopoietic system			√			√	√
decreased CD8-positive, alpha-beta T cell number			√			√	√
increased immunoglobulin level						√	√
homeostasis/metabolism		√	√			√	√
increased insulin secretion						√	√
decreased circulating thyroxine level						√	√
decreased circulating follicle stimulating hormone level		√
decreased circulating luteinizing hormone level		√
pulmonary edema			√			√	√
increased oxygen consumption						√	√
abnormal glucose tolerance						√	√
increased urine antidiuretic hormone level						√	√
decreased urine osmolality						√	√
immune system			√	√	√	√	√
decreased CD8-positive, alpha-beta T cell number			√			√	√
increased immunoglobulin level						√	√
increased autoantibody level				√	√
increased anti-nuclear antigen antibody level						√	√
glomerulonephritis						√	√
lung inflammation			√			√	√
interstitial pneumonia			√			√	√
limbs/digits/tail			√			√	√
abnormal digit development			√			√	√
mortality/aging	√	√	√	√	√	√	√
premature death	√	√
postnatal lethality, complete penetrance			√
perinatal lethality				√	√
perinatal lethality, incomplete penetrance			√			√	√
muscle			√			√	√
heart right ventricle hypertrophy			√			√	√
nervous system						√	√
decreased brain weight						√	√
renal/urinary system						√	√
increased urine antidiuretic hormone level						√	√
decreased urine osmolality						√	√
abnormal renal glomerulus morphology						√	√
glomerulonephritis						√	√
renal glomerular immunoglobulin deposits						√	√
reproductive system		√		√	√	√	√	N
reproductive system phenotype		N						N
oligozoospermia							√
teratozoospermia							√
abnormal sperm flagellum morphology							√
globozoospermia							√
abnormal spermatid morphology							√
decreased spermatid number		√
abnormal spermatocyte morphology		√
multinucleated giant male germ cells		√
increased male germ cell apoptosis		√					√
immotile sperm							√
absent corpus luteum						√
small ovary						√
abnormal seminiferous tubule morphology		√
abnormal seminiferous tubule epithelium morphology							√
small seminiferous tubules		√
abnormal Sertoli cell development		√
abnormal adult Leydig cell differentiation		√
decreased Leydig cell number		√
decreased testis weight							√
decreased testes secretion		√
thin uterus						√
arrest of spermatogenesis		√
arrest of male meiosis		√
anovulation						√
abnormal estrous cycle						√
absent estrous cycle						√
female infertility				√
reduced female fertility						√
male infertility		√			√		√
respiratory system			√	√	√	√	√
pulmonary edema			√			√	√
lung inflammation			√			√	√
interstitial pneumonia			√			√	√
hyperpnea				√	√
vision/eye			√	√	√	√	√	N
vision/eye phenotype								N
abnormal lacrimal gland morphology				√	√
ocular hypotelorism				√	√
microphthalmia			√			√	√
abnormal eyelid morphology				√	√
eyelids fail to open			√	√	√	√	√

View phenotypes and curated references for all genotypes (concatenated display).

Disease models

Key:

√

disease model

expected model not found

Models:

Human Diseases	hm4
nephrogenic diabetes insipidus IDs nephrogenic diabetes insipidus DOID:12387 ICD10CM:N25.1 ICD9CM:588.1 MESH:D018500 NCI:C84919 ORDO:223 UMLS_CUI:C0162283 Close	√

Expression

In Mice Carrying this Mutation:	7 assay results 3 RNA-Seq or microarray experiment(s)
In Structures Affected by this Mutation:	22 anatomical structure(s)

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 Sirt1 Mutation:	81 strains or lines available

References

Original:	J:81010 McBurney MW, et al., The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol. 2003 Jan;23(1):38-54
All:	71 reference(s)

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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