scholarly journals Genetic background influences the impact of KLOTHO deficiency

2020 ◽  
Vol 52 (10) ◽  
pp. 512-516
Author(s):  
Jawad S. Salloum ◽  
Diane E. Garsetti ◽  
Melissa B. Rogers
Keyword(s):  
Genetic Background ◽  
Genetic Architecture ◽  
Disease Susceptibility ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Disease Models ◽  
Inbred Mouse Strains ◽  
Metabolic Interactions ◽  
Klotho Protein ◽  
The Impact

Genetic background is a key but sometimes overlooked factor that profoundly impacts disease susceptibility and presentation in both humans and disease models. Here we show that deficiency of KLOTHO protein, an important renal regulator of mineral homeostasis and a cofactor for FGF23, causes different phenotypes in 129S1/SvlmJ (129) and C57BL/6J (B6) mouse strains. The 129 strain is more severely affected, with decreased longevity, decreased body weight, and increased amounts of kidney calcification compared with B6 mice. Reciprocal F1 crosses of the strains also indicate a parentage effect on the Klotho phenotype with F1 KLOTHO-deficient progeny of B6 mothers and 129 fathers having more kidney calcification than progeny of 129 mothers and B6 fathers. Comparing and contrasting the genetic architecture leading to different phenotypes associated with specific inbred mouse strains may reveal previously unrecognized and important metabolic interactions affecting chronic kidney disease.

New tools for defining the 'genetic background' of inbred mouse strains

2007 ◽  
Vol 8 (7) ◽  
pp. 669-673 ◽  
Author(s):  
William M Ridgway ◽  
Barry Healy ◽  
Luc J Smink ◽  
Dan Rainbow ◽  
Linda S Wicker
Keyword(s):  
Genetic Background ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains

scholarly journals Mndal, a new interferon-inducible family member, is highly polymorphic, suppresses cell growth, and may modify plasmacytoma susceptibility

Blood ◽  
2009 ◽  
Vol 114 (14) ◽  
pp. 2952-2960 ◽  
Author(s):  
Ke Zhang ◽  
Daniel Kagan ◽  
Wendy DuBois ◽  
Richard Robinson ◽  
Valery Bliskovsky ◽  
...  
Keyword(s):  
Cell Growth ◽  
Disease Susceptibility ◽  
Inbred Mouse ◽  
Ectopic Expression ◽  
Modifier Gene ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Differentiation Antigen ◽  
Nuclear Differentiation ◽  
Cluster A

The human HIN-200 gene cluster and its mouse counterpart, the interferon inducible-200 (Ifi200) family, both on Chr 1, are associated with several diseases, including solid tumors and lupus. Our study was initiated to identify the modifier gene(s) encoded by the Pctm locus, in which mouse B-cell plasmacytomas induced by pristane are associated with heterozygosity of Chr 1 genes near the Ifi200 cluster. A screen for differentially expressed genes in granulomatous tissues induced by pristane in resistant and susceptible strains identified a new Ifi200 member whose expression was 1000-fold higher in the strain carrying the resistant allele of Pctm and was the most highly expressed Ifi200 gene. The gene, designated Mndal (for MNDA-like, myeloid nuclear differentiation antigen-like), was absent in the susceptible genome, as were genomic sequences upstream of Ifi203, the gene adjacent to Mndal. Ectopic expression of MNDAL suppressed cell growth, which, together with the disease susceptibility of heterozygotes at the Pctm locus, suggests that Mndal, perhaps with Ifi203, acts as a tumor suppressor and display(s) haploinsufficiency. Mndal is highly polymorphic among inbred mouse strains, because it is absent in 10 of 24 strains. This polymorphism may have implications for other disease modifiers mapping to the same region.

scholarly journals The Effect of Population Structure on Murine Genome-Wide Association Studies

2020 ◽  
Author(s):  
Meiyue Wang ◽  
Gary Peltz
Keyword(s):  
Population Structure ◽  
Association Studies ◽  
Inbred Mouse ◽  
Genome Wide Association ◽  
Mouse Strains ◽  
Genome Wide Association Studies ◽  
Inbred Mouse Strains ◽  
Minimal Impact ◽  
Genome Wide ◽  
The Impact

AbstractPopulation structure (PS) has been shown to cause false positive signals in genome-wide association studies (GWAS). Since PS correction is routinely used in human GWAS, it was assumed that it should be utilized for murine GWAS. Nevertheless, there are fundamental differences between murine and human GWAS, and the impact of PS on murine GWAS results has not been thoroughly investigated. We examined 8223 datasets characterizing biomedical responses in panels of inbred mouse strains to assess the impact of PS on murine GWAS. Surprisingly, we found that PS had a minimal impact on datasets characterizing responses in ≤20 strains; and relatively little impact on the majority of datasets characterizing >20 strains. Moreover, there were examples where association signals within known causative genes could be rejected if PS correction methods were utilized. PS assessment should be carefully used, and considered in conjunction with other criteria, for assessing the candidate genes that are identified in murine GWAS.

scholarly journals THE Ah PHENOTYPE. SURVEY OF FORTY-EIGHT RAT STRAINS AND TWENTY INBRED MOUSE STRAINS

Genetics ◽  
1982 ◽  
Vol 100 (1) ◽  
pp. 79-87
Author(s):  
Daniel W Nebert ◽  
Nancy M Jensen ◽  
Hisashi Shinozuka ◽  
Heinz W Kunz ◽  
Thomas J Gill
Keyword(s):  
Specific Activity ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Mouse Strains ◽  
Ah Receptor ◽  
Inbred Mouse Strains ◽  
Sprague Dawley ◽  
Rat Strains ◽  
Specific Activities ◽  
Inbred Rat

ABSTRACT Forty-four inbred and four randombred rat strains and 20 inbred mouse strains were examined for their Ah phenotype by determining the induction of liver microsomal aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity (EC 1.14.14.1) by intraperitoneal treatment with either β-naphthoflavone or 3-methylcholanthrene. All 48 rat strains were found to be Ah-responsive. The maximally induced hydroxylase specific activities of the ALB/Pit, MNR/Pit, MR/Pit, SHR/Pit, and Sprague-Dawley strains were of the same order of magnitude as the basal hydroxylase specific activities of the ACI/Pit, F344/Pit, OKA/Pit, and MNR/N strains. Six of the 20 mouse strains were Ah-nonresponsive (i.e. lacking the normal induction response and presumably lacking detectable amounts of the Ah receptor). The basal hydroxylase specific activities of the BDL/N, NFS/N, STAR/N, and ST/JN mouse strains were more than twice as high as the maximally induced hydroxylase specific activity of the CBA/HT strain.——To date, 24 Ah-nonresponsive mouse strains have been identified, out of a total of 68 known to have been characterized. The reasons for not finding a single Ah-nonresponsive inbred rat strain—as compared with about one Ah-nonresponsive inbred mouse strain found for every three examined—remain unknown.

scholarly journals Relationship between phospholipid transfer protein activity and HDL level and size among inbred mouse strains

1999 ◽  
Vol 40 (2) ◽  
pp. 295-301 ◽  
Author(s):  
John J. Albers ◽  
Wendy Pitman ◽  
Gertrud Wolfbauer ◽  
Marian C. Cheung ◽  
Hal Kennedy ◽  
...  
Keyword(s):  
Inbred Mouse ◽  
Mouse Strains ◽  
Phospholipid Transfer Protein ◽  
Inbred Mouse Strains ◽  
Protein Activity ◽  
Transfer Protein ◽  
Phospholipid Transfer
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