Home - Australian Phenome Bank

Mouse Strain information

APB ID

8547

Added

06/08/2018

Last Edited

06/08/2018

Strain nomenclature:

C57BL/6-Alms1foz Pparaem1Anu/AnuApb

Nickname:

Foz:Ppara

Genetics

Strain Types

Mutant strain

Genetic Details

CRISPR targeted
Spontaneous

Mode of Inheritance

Recessive

1. Affected Gene Name: Alstrom syndrome 1 homolog (human)

Chromosome	6
Affected Gene Symbol	Alms1
Protein expression of altered gene:	Unknown
Genetic alteration of gene:	There is an 11bp truncating mutation at base 3918 of the Alms1 gene (exon 8).
Location on chromosome (bp):	85537525-85652747 bp, + strand (From VEGA annotation of NCBI Build 37)
MGI Gene Accession ID Please also use this link to determine if other mutants have been registered with MGI (Mouse Genome Informatics)	MGI:1934606
Allele Name	Alstrom syndrome 1 homolog (human); fat aussie
Allele Symbol	Alms1foz
MGI Allele Accession ID	MGI:3621984

2. Affected Gene Name: peroxisome proliferator activated receptor alpha

Chromosome	15
Affected Gene Symbol	Ppara
Protein expression of altered gene:	Unknown
Genetic alteration of gene:	CRISPR/Cas9 mediated mutation
Location on chromosome (bp):	85734983-85802819 bp, + strand (From VEGA annotation of GRCm38)
MGI Gene Accession ID Please also use this link to determine if other mutants have been registered with MGI (Mouse Genome Informatics)	MGI:104740
Synonyms	4933429D07Rik, Nr1c1, Ppar, PPARalpha, PPAR-alpha

Mutant Construction Technique

None

Phenotype

Phenotype Homozygous State

Foz are hyperphagic leading to obesity. Males are sterile. High fat feeding accelerates obesity development, and leads to nonalcoholic steatohepatitis which progresses to liver fibrosis. Steatohepatitis also develops in chow-fed animals. Hyperglycemia: female mice are diabetic by 200 days of age. Increased circulating insulin level: female mice develop insulinemia (20ng/mL insulin vs. 2-5ng/mL in wild-type). Insulin resistance: female mice develop insulin resistance by 200 days of age. Increased eating behavior: mutants eat more than wild-type. Abnormal hepatocyte morphology: mutant livers show many hepatocytes with ballooning degeneration and extensive lobular inflammation with polymorphs and mononuclear cells. Enlarged liver: mice fed high-fat diet show hepatomegaly compared to wild-type (8.9g vs. 2g). Increased liver weight: liver weights in mutant are twice that of wild-type (3.4g vs. 1.6g). Liver fibrosis: mutant livers show pericellular and pericentral fibrosis. Hepatic steatosis: chow-fed mutants develop steatosis; mutants fed the high-fat diet develop severe steatohepatitis.

Phenotype Heterozygous State

Normal

Original Genetic Background

NOD

Genetic Background Currently Maintained

C57BL/6

Coat Colour

Black

Strain identification

How is this strain characterised?

Genotyping

Fertility and Strain maintenance

Fertility and Strain maintenance

	Female	Male
Are homozygous mice viable?	Yes	Yes
Are homozygous mice fertile?	Unknown	No
*Are heterozygotes / hemizygotes fertile?**	Yes	Yes
* Hemizygote as used here refers to males carring a mutation on the X chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Generations Backcrossed	>10
Mating Scheme	heterozygote mating
Homozygous Matings Required?	No
Development Summary	normal weight at birth, obesity develops from 6-8 weeks of age.
Male Fertility Compromised?	Yes
Average Number of Pups at Birth	6.0
Average Number of Pups Surviving to Weaning	5.0
Breeding Performance	Good

Relevant bibliographic / database references

Strain Specific References

Other Related References

General information

Associated IP rights?

Unknown

Does it Model a Human Condition?

Yes

Description of human condition:

Alstrom syndrome is a disorder of childhood obesity, diabetes development and infertility.

Research value of this Strain

When fed a high fat diet foz/foz mice develop nonalcoholic steatohepatitis, a common liver disease that can progress to cirrhosis and liver cancer. There are few animal models of steatohepatitis that show both the liver injury and metabolic phenotype; foz/foz mice are one of the best models so far described. On the C57 background the development of fibrosis is more severe, and nonalcoholic steatohepatitis also develops in chow-fed animals The mouse is also valuable for studying Alstrom syndrome, as well as pathogenesis of obesity and diabetes. It is also of use for studying cilia pathologies as the protein appears to be involved with cilia.

Applicable Research Areas

Metabolism
Diabetes
Gastrointestinal
Obesity
Cardiovascular
Internal/organ

Keywords

obesity
diabetes
nonalcoholic fatty liver disease
alstrom syndrome
cilia

Is the strain available in any form to other researchers

Yes

APB stock stored as:

Cryopreserved sperm (from 5 mice)

Are live mice available?

Yes

MTA needs to be signed?

Yes