A histological study of the hph-1 mouse mutant: an animal model of phenylketonuria and infantile hypertrophic pyloric stenosis.
OBJECTIVE
To quantify the chronological sequence of changes in the morphology and immunoreactivity for neurotransmitters in the pylorus of an animal model of infantile hypertrophic pyloric stenosis and phenylketonuria.


METHODS
Thirty specimens of pylorus from hph-1 mice and age/sex matched controls (age range: 10-180 days) were examined using conventional histology and immunohistochemistry for a variety of antigens: protein gene product 9.5, a pan neuronal marker; vasoactive intestinal polypeptide; nitric oxide synthase two antigens coalesced to the same inhibitory neurons in humans; substance P, a potent excitatory neurotransmitter; and calcitonin gene related peptide, a neurotransmitter implicated in the somatic afferent innervation of the stomach. The changes in the morphology of the muscle layers were quantified and statistically analysed for each age group (10, 20, 40, 90 and 180 days).


RESULTS
Between 10 and 90 days of age, all muscle layers of the hph-1 mice were hypertrophied, for example, 10 days, hph-1 longitudinal muscle mean diameter = 3.4, control = 1.8; hph-1 circular muscle width = 11.5, control = 4.7. The hph-1 mice were significantly smaller during this period (40 days, hph-1 weight = 10 g, control = 25 g). There was no change in the pattern of expression of the antigens examined within the hph-1 mice compared with the controls.


CONCLUSIONS
Hph-1 mice develop a transient smooth muscle hypertrophy of the pylorus attended by gastric distension and failure to gain weight. These changes resolve as the pyloric muscle hypertrophy resolves.
Abel
R M
RM
Department of Paediatric Surgery, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK.
Dorè
C J
CJ
Bishop
A E
AE
Facer
P
P
Polak
J M
JM
Spitz
L
L
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D007150:Immunohistochemistry / Q000662:veterinary; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009130:Muscle, Smooth / Q000473:pathology*; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000235:genetics; D010661:Phenylketonurias / Q000473:pathology*; D011707:Pyloric Stenosis / Q000473:pathology*; D011708:Pylorus / Q000473:pathology
D000941:Antigens; D018377:Neurotransmitter Agents; D006136:GTP Cyclohydrolase