| Gene: 1112 | Name: Kcnq2 | Family: Channel | Subfamily: Potassium | Accession: NM_010611 | GI: 6754437 |
|---|
Gene 1112
Summary of Phenotypic Analysis
Changes related to genotype:
There were no other significant differences detected in the heterozygous mutant animals when compared with age- and gender-matched wild-type control mice.
Weaned progeny from the heterozygous matings were genotyped. No
N0F2 and rare N1F2 homozygous mutant mice were identified by PCR, whereas
wild-type and heterozygous mutant mice were frequently present. The genotypic
ratio suggested an embryonic lethal phenotype.
ES cells derived from the 129/OlaHsd mouse substrain were used to generate
chimeric mice. F1 mice were generated by breeding with C57BL/6 females. F2
heterozygous mutant mice were produced by intercrossing F1 heterozygous males
and females. Additionally, N0F1 heterozygotes were backcrossed to C57BL/6
mice to generate N1F1 heterozygotes. N1F2 homozygous mutant mice were
then produced by intercrossing F1N1 heterozygous males and females.
Wild-type control mice and heterozygous mutant mice were evaluated by the following examinations or tests:
Certain differences, including increased fat percentage by densitometry, were present that occasionally occur spontaneously in mice of this sex and age group. In this target, such differences were present in 2 of 3 heterozygous males. We have not reported these findings as phenotypic changes, but we have presented them here for your consideration.
Gene
1112
Behavior
Heterozygous
mutant and wild-type control mice were evaluated for phenotypic changes by
testing on seven behavioral tasks: Open field test, Tail suspension test,
Rotarod test, Startle response/PPI test, Tail flick test, Hot plate test, and
Metrazol test.
Mouse ID numbers are as follows for the N1 generation:
10 heterozygous mutant males (356273, 356276, 356279, 358151, 358152, 358987,
358988, 358993, 358999, 359001)
27 wild-type control males (353771, 356278, 357078, 357079, 357466, 357467,
358493, 358714, 358985, 358992, 358995, 359024, 359332, 359338, 360452, 360460,
360466, 360723, 360891, 360904, 361424, 363605, 364007, 364018, 364032, 366598,
366954)
ES cells derived from the 129/OlaHsd
mouse substrain were used to generate chimeric mice. F1 mice were
generated by breeding with C57BL/6 females. The resultant F1N0 heterozygotes
were backcrossed to C57BL/6 mice to generate F1N1 heterozygotes. F2N1
heterozygous mutant mice were produced by intercrossing F1N1 heterozygous males
and females.
Behavior Findings:
When compared to age- and gender-matched wild-type control mice, heterozygous
mutant mice required a significantly lower dose of metrazol to reach
various seizure stages, indicating a possible higher propensity towards seizure
phenotype.
There
were no other genotype-related differences noted between heterozygous mutant
and wild-type control mice for any other parameters evaluated during behavior
testing.
Gene 1112
Expression
Summary
Taqman Summary:
The highest levels of RNA transcripts are detectable in whole brain, cortex,
subcortical region, cerebellum, brainstem, olfactory bulb, spinal cord,
pituitary gland and adrenal gland.
Lower levels of RNA transcripts are also detectable in eye, thymus, lymph nodes, gallbladder, stomach, small intestine, cecum, colon, testis, epididymis, prostate gland, ovary and white fat.
No RNA transcripts are detectable in Harderian glands, heart, lung, liver, pancreas, kidney, spleen, bone marrow, skin, urinary bladder, salivary gland, skeletal muscle, tongue, seminal vesicle, coagulating gland and uterus.
LacZ Summary:
LacZ expression was not detected in any of the organs or tissues
examined: brain, spinal cord, sciatic nerve, eyes, thymus, spleen, lymph
nodes, bone marrow, aorta, heart, lung, liver, pancreas, kidney, urinary
bladder, parathyroid gland, thyroid gland, pituitary gland, adrenal glands,
skeletal muscle, skin, testis, prostate gland, ovary, uterus and cervix.
Gene 1112
Densitometry
There were no significant differences detected in the heterozygous mutant mice
when compared with age- and gender-matched wild-type control mice.
The following mice were evaluated by dual-energy x-ray absorptiometry.
49
Day Cohort Mouse ID numbers are as follows:
2 heterozygous mutant females (308100, 313770)
3 heterozygous mutant males (298467, 298468, 313769)
2 wild-type control females (293263, 298469)
2 wild-type control males (319728, 323609)
Bone Mineral Density (BMD in g/cm2 ), fat % (fat percentage
expressed as a percentage of body soft tissue compartment), and R-value of soft
tissue were calculated from Bone Mineral Content (BMC in g), bone and tissue
areas (cm2 ), and total tissue mass
(g) generated by a PIXImus densitometer.
Densitometric Findings:
Certain densitometric differences between mice, including increased fat
percentage, were present that occasionally occur spontaneously in this age
group. In this target, such differences were present in 2 of 3 heterozygous
males (298467, 313769). We have not reported these findings as phenotypic
changes, but we have presented them here for your consideration.
Gene 1112
Histopathology
There were no significant differences detected in the heterozygous mutant mice
when compared with age- and gender-matched wild-type control mice.
Tissues from the following mice were evaluated histologically.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (302224, 308100, 313770)
3 heterozygous mutant males (298467, 298468, 313769)
2 wild-type control females (293263, 298469)
2 wild-type control males (319728, 323609)
No Significant Abnormalities:
The following tissues were examined and considered to have no genotype-related abnormality: brain, pituitary gland, ears, nasal cavity, salivary glands, oral cavity, lymph nodes, aorta, lungs, liver, gallbladder, pancreas, spleen, kidneys, urinary bladder, stomach, small and large intestines, larynx, esophagus, trachea, thyroid gland, thymus gland, tongue, skeletal muscle, sciatic nerve, mammary glands, vertebrae, spinal cord, bone (skull, sternum, femur, tibia, and stifle joint), reproductive tract (including gonads), eyes, Harderian glands, integumentary system (skin and either clitoral or preputial glands), and bone marrow.
Bone
marrow was examined in sections of sternum, vertebrae, and/or femur and tibia.
Marrow cellularity, myeloid:erythroid (M:E) ratio, myeloid and erythroid
maturation sequences, and numbers of megakaryocytes were evaluated.
Incidental lesions were present in some tissues. These findings were
considered to represent background lesions occasionally seen in this strain of
mice, lesions due to spontaneous disease, age-related lesions, and/or lesions
of a nonspecific etiology. They were not considered to be genotype related.
Gene 1112
Necropsy
There were no significant differences detected in the heterozygous mutant mice when compared with age- and gender-matched wild-type control mice.
The following mice were necropsied. Body weight, body length, and organ weights were obtained, and gross pathological findings were recorded.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (302224, 308100, 313770)
3 heterozygous mutant males (298467, 298468, 313769)
2 wild-type control females (293263, 298469)
2 wild-type control males (319728, 323609)
Mice were examined for the following observables: adrenal glands, body length,
body weight, bone marrow, bone - cranium, bone - femur, bone - sternum, bone -
stifle joint, bone - vertebral column, brain, cecum, colon, duodenum,
epididymis - seminal vesicle, esophagus, eyes, gallbladder, general appearance,
Harderian glands, heart, heart weight, ileum, jejunum, kidney weight, kidneys,
liver, liver weight, lungs, lymph nodes, mesentery, ovaries, pancreas, penis,
salivary glands, sciatic nerve, scrotum, skeletal muscle, skin, skinned mouse,
spleen, spleen weight, stomach, testes, testes - epididymis weight, thymus,
thymus weight, tongue, trachea, urinary bladder, urine, uterus, and vagina.
(Gender-specific observables apply to the appropriate gender.)
Necropsy Findings:
There were no genotype-related or biologically significant differences noted between mutant and wild-type control mice for any of the parameters evaluated at necropsy. Incidental lesions were present in some tissues. These findings were considered to represent background lesions occasionally seen in this strain of mice, lesions due to spontaneous disease, age-related lesions, and/or lesions of a nonspecific etiology. They were not considered to be related to genotype.
Body and Organ Weight Findings:
Differences in body length, body weight, organ weights, and/or organ weight to body weight ratios were present between individual mice. The variability between mice usually fell within our historical reference ranges and was not correlated with genotype.
Gene 1112
Clinical Chemistry
There
were no significant differences in the heterozygous mutant mice when
compared with age- and gender-matched wild-type control mice.
Serum
samples from the following mice were evaluated by a clinical chemistry panel.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (302224, 308100, 313770)
3 heterozygous mutant males (298467, 298468, 313769)
2 wild-type control females (293263, 298469)
2 wild-type control males (319728, 323609)
Values for the various analytes evaluated were generally similar
between heterozygous mutant and wild-type control mice. Although
variations in clinical chemistry values were present in some mice, they were
not related to genotype and, thus, were not considered phenotypically relevant.
Gene 1112
Hematology
There
were no significant differences in the heterozygous mutant mice when
compared with age- and gender-matched wild-type control mice.
Blood
samples from the following mice were evaluated by a complete blood count and
differential cell count.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (302224, 313770, 323607)
3 heterozygous mutant males (298467, 298468, 313769)
2 wild-type control females (293263, 298469)
2 wild-type control males (319728, 323609)
Although minor variations of hematological values were present in some mice,
these changes were not related to genotype and, thus, were not considered
phenotypically relevant.
Gene 1112
Physical Examination
There were no significant
differences detected in the heterozygous mutant mice when compared with age-
and gender-matched wild-type control mice.
The
following mice were evaluated by physical examination.
49
Day Cohort Mouse ID numbers are as follows:
3 heterozygous mutant females (302224, 308100, 313770)
3 heterozygous mutant males (298467, 298468, 313769)
2 wild-type control females (293263, 298469)
2 wild-type control males (319728, 323609)
Mice were examined in detail as follows: anus, behavior, body shape, claws,
coat - fur, coat color - back, coat color - belly, ear - left, ear - right, eye
- left, eye - right, eye color - left, eye color - right, feces, forelimb -
left, forelimb - right, forelimb number of amputated digits - left, forelimb
number of amputated digits - right, forelimb number of digits - left, forelimb
number of digits - right, general appearance, genitals - female, genitals -
male, hair type, head shape, hindlimb - left, hindlimb - right, hindlimb number
of amputated digits - left, hindlimb number of amputated digits - right,
hindlimb number of digits - left, hindlimb number of digits - right, injuries,
lesions, limb shape, locomotor, lumps - masses, mammary glands, mice in cage,
respiration, skin appearance, snout, swelling - joints, tail, teeth color,
teeth length, urine, and whiskers. (Gender-specific observables apply to the
appropriate gender.)
Individual heterozygous mutant mice had only occasional minor differences in observed physical features compared to wild-type control mice. These findings were considered to represent individual variability, background features occasionally seen in this strain of mice, findings due to spontaneous disease, age-related findings, and/or findings of a nonspecific etiology. However, none of these differences were regarded as biologically significant or genotype related.