Cryptosporidium infections in inbred strains of mice.

Cryptosporidium, a protozoan parasite of man and animals, is an important etiological agent of diarrhea throughout the world, particularly in children and immunocompromised individuals such as AIDS patients. Unfortunately, because of the lack of both in vivo laboratory models and reliable in vitro parasite culture systems, virtually nothing is known about the immunological events occurring during disease. In order to identify reliable animal models for infection, we studied C. parvum infections in 19 different strains of mice representing 12 H-2 haplotypes: A/J, AKR/J, B10.D2/J, B10.M/J, C3H/HeJ, C57BL/65, C57BL/6J-bgJ, CBA/NJ, DBA/1J, DBA/2J, HRS/J, HTG/J, NZB/B1NJ, NZW/J, P/J, RIII/J, SJL/J, SWR/J, and WB/ReJ, and in one gerbil: Meriones unguiculatus. Fecal samples and histological sections of the intestine taken on day 7 post-Cryptosporidium inoculation indicated that only the beige mouse (C57BL/6J-bgJ) harbored significant numbers of parasites compared to the other strains. The numbers of parasites harbored in these NK cell-deficient beige mice were, however, considerably lower than those seen in neonatal mice. Adult inbred mouse strains susceptible to Cryptosporidium infections are discussed.     

Variations in serum calcium between strains of inbred mice.

Serum calcium concentrations of C3H/Fg, C3H/HeJFg, AKR/Fg, A/Fg, and LCS/Fg mice were compared at 4 and 7 mo of age. In the C3H/Fg and A-strain mice, calcium levels did not differ significantly between the 2 strains nor between the 2 age groups. The C3H/HeJFg, LCS/Fg, and C57BL/Fg strains formed a distinct group with similar calcium levels, but at a significantly higher level than C3H/Fg and A/Fg group. Again there was no significant difference between the 4- and 7-mo groups. The AKR/Fg strain was distinct from both groups in that higher calcium levels characteristic of the second group (C3H/HeJFg, LCS/Fg, and C57BL/Fg, were seen at 4 mo of age, but lower calcium levels similar to those of the C3H/Fg and A/Fg strains were found at 7 mo of age.     

Impulsive choice in inbred strains of mice

When humans or non-humans are given a choice between receiving a sooner-smaller (SS) reinforcer, or a later-larger (LL) reinforcer, the choice of a SS reinforcer represents impulsive choice whereas the choice of a LL reinforcer represents self-controlled choice. It has been suggested that both biological and genetic factors influence impulsive/self-control choice in this paradigm. In the present study, the inbred strains of BALB/c, C57BL/6, and DBA/2 mice were given a choice to press one of two levers in an operant chamber. Depending on their choice, mice received either a smaller reinforcer (one pellet delivered after 6s) sooner (SS) or a larger reinforcer (two pellets after 6, 9, 12, 18, or 30s) later (LL). Mice preference for the larger reinforcer decreased with longer delays. More importantly, the BALB/c mice chose the SS reinforcer more often than the C57BL/6 mice under the 9- and 12-s delays, and more often than the DBA/2 mice under the 9-s delay. This indicates that the choice pattern of the BALB/c strain is more "impulsive" than the other strains and suggests that specific gene configurations influence impulsive choice in mice.     

Quiet mutations in inbred strains of mice

The year 2009 is the 100th anniversary of the founding of the first inbred strain of mouse, called DBA. During the last 100 years, inbred strains have proved their value for biomedical research and the number of such strains has mushroomed to over 450, each with different genotypic and phenotypic characteristics and useful for the study of disease and normal function. However, although inbred strains are stable, they are not fixed entities and researchers need to be aware of the phenomena of new mutations and of genetic drift, which occur within all mouse colonies. If the mutations are what we term in this review 'quiet mutations', then they might result in rather unexpected and sometimes tremendously valuable results. Here, we discuss these phenomena and look at how new genomic technologies might help us to detect 'quiet mutations' and use them to our advantage.     

Identification of inbred strains of mice,Mus musculus. I. Genetic control of inbred strains of mice using starch gel electrophoresis

Fifteen biochemical markers were tested in 30 inbred strains of mice to control the genetic constitution of each strain. Discrepancies in pattern from Standardized Nomenclature for Inbred Strains of Mice are reported and discussed.This work was supported by Grant No. 512–2532 from the Danish Medical Research Council.     

Sex ratio of inbred strains of mice

A study of the sex ratio in mice of the inbred strains (CBA and C3H) and connection of the postimplantation embryonic mortality in mice of these strains with the sex distribution of embryos demonstrated that the sex ratio in these mice was 1:1. Literature and the author's personal data suggested that genetic features of mice of the inbred strains failed to influence significantly the sex ratio of the offspring. The postimplantation embryonic death rate in the C3H mice exceeded that in the CBA mice (14.4 and 9.3%, respectively). However, the balanced sex ratio in mice of these strains points to the absence of selective mortality of the embryos of any one sex during embryogenesis.     

DNA sequence variation within the beta-glucuronidase gene complex among inbred strains of mice

Tightly linked to the gene that encodes murine beta-glucuronidase (GUS) are three GUS-specific regulatory elements. Together, these elements define the GUS gene complex. Specific alleles of each regulatory element are associated with a specific GUS structural allele. These associations define the three common forms (haplotypes) of the GUS gene complex, designated A, B, and H. As an initial step in defining the DNA determinants of each regulatory element and to develop DNA markers for the common haplotypes, we have identified several DNA variants by blot hybridization analysis of restricted genomic DNA using GUS-specific cDNA probes. Of 30 tested restriction endonucleases, 24 reveal DNA polymorphisms that distinguish B- and H-haplotype DNA from that of the A haplotype. Of these 24, 18 uncover a restriction fragment length polymorphism in which the polymorphic fragment of A-haplotype DNA is 200-300 bp larger than the corresponding fragment of B- or H-haplotype DNA. DNA sequence analysis of this polymorphic region reveals the presence of a short, interspersed repetitive element of the B2 family within A-haplotype DNA which is absent in DNAs of B- or H-haplotype mice. None of the DNA variations revealed by these analyses can be associated at this time with variation in the regulatory or structural properties of GUS among the common haplotypes. Nevertheless, they do provide useful haplotype-specific markers within the GUS gene complex which are of critical importance for DNA transfer experiments in transgenic mice and in cultured cells.     

Egg production of Clonorchis sinensis in different strains of inbred mice.

In order to compare the intraspecific variation in host-parasite relationship of Clonorchis sinensis, six strains of inbred mice, ICR, DDY, GPC, BALB/c, nude and DS, were infected orally with 20 metacercariae of C. sinensis. The biologic incubation period of C. sinensis was the shortest in DDY mice, 21.2 days in average, followed by GPC 21.4, BALB/c and DS 23.2, ICR and nude 23.4 days, respectively. The fertile period of the fluke was also the longest in the DDY strain, 164 days on average, followed by GPC 132, BALB/c 97, nude 37, DS 32 and ICR 28 days. The egg-laying capacity of the fluke in DDY and GPC was relatively high and stable compared with the other four strains of mice. It was found that there are intraspecific variations in biologic incubation period, fertile period, and fecundity of C. sinensis. The DDY mouse is likely to be the most suitable experimental animal among the six strains of the mice tested.     

Random sequence oligonucleotide primers detect polymorphic DNA products which segregate in inbred strains of mice

The random amplification of polymorphic DNA (RAPD) using primers of arbitrary nucleotide sequence has been extremely valuable in identifying heritable markers in a variety of systems. The present studies examined whether the RAPD technique can identify large numbers of polymorphisms that can be used to construct genetic maps in inbred strains of mice. By screening the inbred mouse strains C57BL/6J and DBA/2J with 481 random 10-mer oligonucleotide primers, we identified 95 polymorphisms and mapped 76 of these by use of the BXD series of recombinant inbred (RI) strains. The results clearly demonstrate that the RAPD technique allows for the identification of large numbers of DNA-based polymorphisms that distinguish these two inbred strains of mice,and that such markers can readily be used to construct molecular genetic linkage maps.     

Ganglioside compositions of erythrocytes from various strains of inbred mice. Ocurrence of sialosylgalactosylceramide in red blood cells of inbred mice

The gangliosides from the erythrocytes of various strains of inbred mice were analyzed. The ganglioside compositions differed in different strains and the strains could be divided into 4 types on the basis of this difference. The main ganglioside is GM4 or sialosyl galactosyl ceramide in Type 1, and unidentified ganglioside in Type 2, GM4 and GM2 in almost equal amounts in Type 3, and GM2 in Type 4.     

Enzymes of galactose metabolism in erythrocytes and liver of inbred strains of mice.

This study compares the activity of galactokinase, galactose-1-phosphate uridyltransferase, and UDPgalactose-4-epimerase, the important enzymes in the pathway of conversion of galactose to glucose in red cells and liver of five inbred strains of mice. In the red cells, galactokinase varied over a four-fold range of activity while the other enzymes varied about two-fold. The activity of each of the enzymes varied independently of the other so that red cells of each strain had a unique pattern for the three enzymes. The red cell activity pattern was not reflected in liver tissue which showed little interstrain variation for each of the three enzymes. The ratio of liver galactokinase to uridyltransferase and epimerase was very similar in all five strains. Oxidation in vivo of ¹⁴C galactose to ¹⁴CO₂ was examined in the two strains of mice with the widest divergence of red cell galactokinase activity and no difference was found in this parameter measuring the physiological disposition of the sugar. The wide variation of the red cell enzyme activity appears to have little metabolic consequence for the animal, the oxidation of the sugar reflecting the relative constancy of the liver enzyme activity.